Pharmaceutics

2024

Jump to: 2023, 2022, 2021, 2020

13 pages, 1531 KiB

Open AccessArticle

Sustained-Release Solid Dispersions of Fenofibrate for Simutaneous Enhancement of the Extent and Duration of Drug Exposure

by Seong-Jin Park, Gyu Lin Kim and Hyo-Kyung Han

Pharmaceutics 2024, 16(12), 1617; https://doi.org/10.3390/pharmaceutics16121617 - 20 Dec 2024

Viewed by 343

Abstract

Background/Objectives: A sustained-release formulation of fenofibrate while enhancing drug dissolution with minimal food effect is critical for maximizing the therapeutic benefits of fenofibrate. Therefore, this study aimed to develop an effective solid dispersion formulation of fenofibrate for simultaneous enhancement in the extent and [...] Read more.

Background/Objectives: A sustained-release formulation of fenofibrate while enhancing drug dissolution with minimal food effect is critical for maximizing the therapeutic benefits of fenofibrate. Therefore, this study aimed to develop an effective solid dispersion formulation of fenofibrate for simultaneous enhancement in the extent and duration of drug exposure. Methods: Fenofibrate-loaded solid dispersions (FNSDs) were prepared using poloxamer 407 and Eudragit^® RSPO at varied ratios via solvent evaporation. In vitro/in vivo characteristics of FNSDs were examined in comparison with untreated drugs. Results: Based on dissolution profiles of FNSDs in aqueous media, the weight ratio of fenofibrate: poloxamer 407: Eudragit^® RSPO at 1:1:4 (FNSD2) was selected as the optimal composition for achieving sustained drug release while maximizing the drug dissolution. The enhanced and sustained drug release of FNSD2 was also confirmed in a buffer transition system mimicking the pH change in the gastrointestinal tract. FNSD2 achieved approximately 66% drug release over 12 h, while pure drug exhibited only 12%. Furthermore, FNSD2 maintained similar release rates under fed and fasted conditions, while the entire drug dissolution slightly increased in the fed state. Structural analysis by x-ray diffraction showed that fenofibrate remained crystalline in FNSD2. Pharmacokinetic studies in rats revealed that orally administered FNSD2 significantly improved the extent and duration of systemic drug exposure. Compared to pure drugs, the FNSD2 formulation increased the oral bioavailability of fenofibrate by 22 folds with the delayed T_max of 4 h in rats. Conclusion: FNSD2 formulation is effective in improving the extent and duration of drug exposure simultaneously. Full article

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13 pages, 3134 KiB

Open AccessArticle

Formulation of Ascorbic Acid and Betaine-based Therapeutic Deep Eutectic System for Enhanced Transdermal Delivery of Ascorbic Acid

by Ji-Eun Song, Seung-Hyun Jun, Joo-Yeon Ryoo and Nae-Gyu Kang

Pharmaceutics 2024, 16(5), 687; https://doi.org/10.3390/pharmaceutics16050687 - 20 May 2024

Cited by 1 | Viewed by 1583

Abstract

L-ascorbic acid (AA), a potent antioxidant, is commonly used topically in the pharmaceutical and cosmetic fields. However, the incorporation of AA into topical formulations is difficult because of its highly unstable nature and relatively poor skin permeability. In this study, we propose [...] Read more.

L-ascorbic acid (AA), a potent antioxidant, is commonly used topically in the pharmaceutical and cosmetic fields. However, the incorporation of AA into topical formulations is difficult because of its highly unstable nature and relatively poor skin permeability. In this study, we propose an alternative strategy for improving the solubility and topical delivery of AA through its conversion to a therapeutic deep eutectic system (THEDES). AA and betaine (Bet)-based THEDESs were prepared at certain molar ratios and characterized using polarized optical microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. Solubility tests showed that AA in the form of THEDES was readily soluble in various polyols (glycerin, 1,3-butylene glycol, dipropylene glycol, and 1,3-propanediol) at a high concentration (approximately 40%). Furthermore, compared to AA alone or the physical mixture of AA and Bet, AA-based THEDES significantly enhanced AA delivery through porcine skin. In an in vivo human study, THEDES-containing serum reduced the markers of aging and induced an even skin tone. These findings indicate the utility of AA and Bet-based THEDES as novel transdermal delivery systems for AA. Furthermore, our approach also showed good extension to developing gluconolactone, a well-known natural antioxidant, and Bet-based THEDES, showing potential application in transdermal delivery systems. Full article

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2023

Jump to: 2024, 2022, 2021, 2020

14 pages, 2553 KiB

Open AccessEditor’s ChoiceArticle

Improved Therapeutic Efficacy of MT102, a New Anti-Inflammatory Agent, via a Self-Microemulsifying Drug Delivery System, in Ulcerative Colitis Mice

by Kshitis Chandra Baral, Sang Hoon Lee, Jae Geun Song, Seong Hoon Jeong and Hyo-Kyung Han

Pharmaceutics 2023, 15(12), 2720; https://doi.org/10.3390/pharmaceutics15122720 - 2 Dec 2023

Viewed by 1571

Abstract

MT-102 is a new anti-inflammatory agent derived from Juglans mandshurica and Isatis indigotica. Its therapeutic potential is hindered by low aqueous solubility, impacting its in vivo efficacy. Therefore, this study aimed to develop a self-microemulsifying drug delivery system (SMEDDS) for MT-102 to [...] Read more.

MT-102 is a new anti-inflammatory agent derived from Juglans mandshurica and Isatis indigotica. Its therapeutic potential is hindered by low aqueous solubility, impacting its in vivo efficacy. Therefore, this study aimed to develop a self-microemulsifying drug delivery system (SMEDDS) for MT-102 to enhance its oral efficacy in treating ulcerative colitis. Solubility assessment in different oils, surfactants, and cosurfactants led to a SMEDDS formulation of MT-102 using Capmul MCM, Tween 80, and propylene glycol. Based on a pseudoternary phase diagram, the optimal SMEDDS composition was selected, which consisted of 15% Capmul MCM, 42.5% Tween 80, and 42.5% propylene glycol. The resulting optimized SMEDDS (SMEDDS-F1) exhibited a narrow size distribution (177.5 ± 2.80 nm) and high indirubin content (275 ± 5.58 µg/g, a biomarker). Across an acidic to neutral pH range, SMEDDS-F1 showed rapid and extensive indirubin release, with dissolution rates approximately 15-fold higher than pure MT-102. Furthermore, oral administration of SMEDDS-F1 effectively mitigated inflammatory progression and symptoms in a mouse model of ulcerative colitis, whereas pure MT-102 was ineffective. SMEDDS-F1 minimized body weight loss (less than 5%) without any significant change in colon length and the morphology of colonic tissues, compared to those of the healthy control group. In addition, oral administration of SMEDDS-F1 significantly inhibited the secretion of pro-inflammatory cytokines such as IL-6 and TNF-α. In conclusion, the SMEDDS-F1 formulation employing Capmul MCM, Tween 80, and propylene glycol (15:42.5:42.5, w/w) enhances the solubility and therapeutic efficacy of MT-102. Full article

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2022

Jump to: 2024, 2023, 2021, 2020

14 pages, 4146 KiB

Open AccessEditor’s ChoiceArticle

Alleviation of Surgery-Induced Osteitis in Sinonasal Cavity by Dexamethasone-Loaded Poly(lactic-co-glycolic acid) (PLGA) Microparticles with Strong Calcium-Binding Affinity

by Seung-No Hong, Minjae Kim, Jin-A Park, Minji Kang, Hyunkyung Cha, Sohyun Park, Joon Kon Kim, Jinyoung Pac, Yuju Seo, Sungwhan Kim, Minju Kim, Dae Woo Kim and Yan Lee

Pharmaceutics 2022, 14(3), 546; https://doi.org/10.3390/pharmaceutics14030546 - 28 Feb 2022

Cited by 4 | Viewed by 2846

Abstract

For the treatment of sinus surgery-induced osteitis in chronic rhinosinusitis (CRS), oral or intranasal administration of corticoids is generally used, although it has critical limitations and unavoidable side effects. To overcome these limitations, we designed dexamethasone (Dex)-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles [...] Read more.

For the treatment of sinus surgery-induced osteitis in chronic rhinosinusitis (CRS), oral or intranasal administration of corticoids is generally used, although it has critical limitations and unavoidable side effects. To overcome these limitations, we designed dexamethasone (Dex)-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles with bone-specific binding affinity, which could release the encapsulated Dex in a sustained manner on the exposed bone after the surgical wound in the nasal cavity. In a previous report, we prepared poly(butyl methacrylate-co-methacryloyloxyethyl phosphate) (PBMP) with both calcium-binding phosphomonoester groups and PLGA-binding butyl groups to introduce strong calcium-binding property to PLGA particles. In this study, after successful encapsulation of Dex in the PBMP-coated PLGA particles, we applied the Dex-PLGA/PBMP to the treatment of post-operative osteitis in the sinonasal cavity. The Dex-PLGA/PBMP showed more than 5-times higher binding affinity to the hydroxyapatite (HA) surface compared to the non-coated PLGA particles, without altering the morphology and encapsulation efficiency. After establishing the neo-osteogenesis mouse model by mechanical injury of the nasal mucosa, the activity of intranasally administered Dex-PLGA/PBMP was examined to inhibit the formation of undesirable new woven bone during the wound healing process. In addition, significantly lower osteocalcin activity was observed in the group treated with Dex-PLGA/PBMP, indicating decreased activation of osteoblasts. Overall, these results demonstrate that the PLGA/PBMP microparticle strategy has great potential for the treatment of CRS-related osteitis by localized corticoid delivery on the exposed bones with minimal side effects. Full article

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2021

Jump to: 2024, 2023, 2022, 2020

17 pages, 4042 KiB

Open AccessArticle

Formation of Self-Assembled Liquid Crystalline Nanoparticles and Absorption Enhancement of Ω-3s by Phospholipids and Oleic Acids

by Sang-Won Jeon, Han-Sol Jin and Young-Joon Park

Pharmaceutics 2022, 14(1), 68; https://doi.org/10.3390/pharmaceutics14010068 - 28 Dec 2021

Cited by 5 | Viewed by 2712

Abstract

This study aimed to optimize and evaluate self-assembled liquid crystalline nanoparticles (SALCs) prepared from phospholipids and oleic acid for enhancing the absorption of Ω-3s. We explored the structure and optimal formulation of SALCs, which are composed of Ω-3 ethyl ester (Ω-3 EE), phospholipids, [...] Read more.

This study aimed to optimize and evaluate self-assembled liquid crystalline nanoparticles (SALCs) prepared from phospholipids and oleic acid for enhancing the absorption of Ω-3s. We explored the structure and optimal formulation of SALCs, which are composed of Ω-3 ethyl ester (Ω-3 EE), phospholipids, and oleic acid, using a ternary diagram and evaluated the improvement in Ω-3 dissolution, permeation, and oral bioavailability. The in vitro dissolution and pharmacokinetics of Ω-3 SALCs were compared with those of Omacor soft capsules (as the reference). The shape of the liquid crystal was determined according to the composition of phospholipids, oleic acids, and Ω-3s and was found to be in cubic, lamellar, and hexagonal forms. The dissolution rates of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) obtained from Ω-3 SALCs were 1.7 to 2.3-fold higher than those of the Omacor soft capsules. Furthermore, a pharmacokinetic study in male beagle dogs revealed that Ω-3 SALCs increased the oral bioavailability of Ω-3 EE by 2.5-fold for EPA and 3.1-fold for DHA compared with the reference. We found an optimal formulation that spontaneously forms liquid crystal-based nanoparticles, improving the bioavailability of EPA and DHA, not found in the existing literature. Our findings offer insight into the impact of nanoparticle phase on the oral delivery of oil-soluble drugs and provide a novel Ω-3 EE formulation that improves the bioavailability of EPA and DHA. Full article

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25 pages, 12942 KiB

Open AccessArticle

A Needle-Free Jet Injection System for Controlled Release and Repeated Biopharmaceutical Delivery

by Mojiz Abbas Trimzi and Young-Bog Ham

Pharmaceutics 2021, 13(11), 1770; https://doi.org/10.3390/pharmaceutics13111770 - 22 Oct 2021

Cited by 12 | Viewed by 9327

Abstract

Swift vaccination is necessary as a response to disease outbreaks and pandemics; otherwise, the species under attack is at risk of a high fatality rate or even mass extinction. Statistics suggest that at least 16 billion injections are administered worldwide every year. Such [...] Read more.

Swift vaccination is necessary as a response to disease outbreaks and pandemics; otherwise, the species under attack is at risk of a high fatality rate or even mass extinction. Statistics suggest that at least 16 billion injections are administered worldwide every year. Such a high rate of needle/syringe injection administration worldwide is alarming due to the risk of needle-stick injuries, disease spread due to cross-contamination and the reuse of needles, and the misuse of needles. In addition, there are production, handling, and disposal costs. Needle phobia is an additional issue faced by many recipients of injections with needles. In addition to a detailed literature review highlighting the need for needle-free injection systems, a compressed air-driven needle-free jet injection system with a hydro-pneumatic mechanism was designed and developed by employing an axiomatic design approach. The proposed injection system has higher flexibility, uninterrupted force generation, and provides the possibility of delivering repeated injections at different tissue depths from the dermis to the muscle (depending on the drug delivery requirements) by controlling the inlet compressed air pressure. The designed needle-free jet injector consists of two primary circuits: the pneumatic and the hydraulic circuit. The pneumatic circuit is responsible for driving, pressurizing, and repeatability. The hydraulic circuit precisely injects and contains the liquid jet, allowing us to control the volume of the liquid jet at elevated pressure by offering flexibility in the dose volume per injection. Finally, in this paper we report on the successful design and working model of an air-driven needle-free jet injector for 0.2–0.5 mL drug delivery by ex vivo experimental validation. Full article

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23 pages, 2632 KiB

Open AccessReview

Recent Progress in Drug Release Testing Methods of Biopolymeric Particulate System

by Yejin Kim, Eun Ji Park, Tae Wan Kim and Dong Hee Na

Pharmaceutics 2021, 13(8), 1313; https://doi.org/10.3390/pharmaceutics13081313 - 23 Aug 2021

Cited by 51 | Viewed by 7257

Abstract

Biopolymeric microparticles have been widely used for long-term release formulations of short half-life chemicals or synthetic peptides. Characterization of the drug release from microparticles is important to ensure product quality and desired pharmacological effect. However, there is no official method for long-term release [...] Read more.

Biopolymeric microparticles have been widely used for long-term release formulations of short half-life chemicals or synthetic peptides. Characterization of the drug release from microparticles is important to ensure product quality and desired pharmacological effect. However, there is no official method for long-term release parenteral dosage forms. Much work has been done to develop methods for in vitro drug release testing, generally grouped into three major categories: sample and separate, dialysis membrane, and continuous flow (flow-through cell) methods. In vitro drug release testing also plays an important role in providing insight into the in vivo performance of a product. In vitro release test with in vivo relevance can reduce the cost of conducting in vivo studies and accelerate drug product development. Therefore, investigation of the in vitro–in vivo correlation (IVIVC) is increasingly becoming an essential part of particulate formulation development. This review summarizes the principles of the in vitro release testing methods of biopolymeric particulate system with the recent research articles and discusses their characteristics including IVIVC, accelerated release testing methods, and stability of encapsulated drugs. Full article

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19 pages, 2505 KiB

Open AccessArticle

DoE-Based Design of a Simple but Efficient Preparation Method for a Non-Effervescent Gastro-Retentive Floating Tablet Containing Metformin HCl

by Byungsuk Kim, Youngjoo Byun and Eun Hee Lee

Pharmaceutics 2021, 13(8), 1225; https://doi.org/10.3390/pharmaceutics13081225 - 8 Aug 2021

Cited by 7 | Viewed by 4416

Abstract

A sustained-release non-effervescent floating matrix tablet was prepared using a simple and efficient direct compression of spray-dried granules containing metformin hydrochloride and cetyl alcohol with hydroxypropyl methylcellulose K15M (HPMC K15M). The design of experiments was employed to explore the optimal composition of the [...] Read more.

A sustained-release non-effervescent floating matrix tablet was prepared using a simple and efficient direct compression of spray-dried granules containing metformin hydrochloride and cetyl alcohol with hydroxypropyl methylcellulose K15M (HPMC K15M). The design of experiments was employed to explore the optimal composition of the tablet. The similarity factor was employed to evaluate the equivalence in dissolution profiles between the test tablets and Glucophage XR as a reference. Bootstrap analysis was used to eliminate the formulations for which the dissolution profile was potentially inequivalent to that of the reference. The optimized tablet consisting of 150 mg of cetyl alcohol and 17% HPMC K15M showed a dissolution profile comparable with that of the reference with a similarity factor of 52.41, exhibited a floating lag time of less than 3 s in buffer media, remained floating for 24 h, and reduced the tablet weight by about 20% compared to that of the reference. The current study sheds light on the potential use of non-effervescent gastro-retentive extended-release tablets for high-dose drugs using a simple and efficient direct compression method, and as a potential alternative treatment for Glucophage XR. This study also highlights the importance of a systematic approach to formulation optimization and the evaluation of the dissolution profile. Full article

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20 pages, 2908 KiB

Open AccessArticle

Population Pharmacokinetic Analysis of Cefaclor in Healthy Korean Subjects

by Seung-Hyun Jeong, Ji-Hun Jang, Hea-Young Cho and Yong-Bok Lee

Pharmaceutics 2021, 13(5), 754; https://doi.org/10.3390/pharmaceutics13050754 - 19 May 2021

Cited by 14 | Viewed by 4189

Abstract

The aims of this study were: (1) to perform population pharmacokinetic analysis of cefaclor in healthy Korean subjects, and (2) to investigate possible effects of various covariates on pharmacokinetic parameters of cefaclor. Although cefaclor belongs to the cephalosporin family antibiotic that has been [...] Read more.

The aims of this study were: (1) to perform population pharmacokinetic analysis of cefaclor in healthy Korean subjects, and (2) to investigate possible effects of various covariates on pharmacokinetic parameters of cefaclor. Although cefaclor belongs to the cephalosporin family antibiotic that has been used in various indications, there have been very few population studies on factors affecting its pharmacokinetics. Therefore, this study is very important in that effective therapy could be possible through a population pharmacokinetic study that explores effective covariates related to cefaclor pharmacokinetic diversity between individuals. Pharmacokinetic results of 48 subjects with physical and biochemical parameters were used for the population pharmacokinetic analysis of cefaclor. A one-compartment with lag-time and first-order absorption/elimination was constructed as a base model and extended to include covariates that could influence between-subject variability. Creatinine clearance and body weight significantly influenced systemic clearance and distribution volume of cefaclor. Cefaclor’s final population pharmacokinetic model was validated and some of the population’s pharmacokinetic diversity could be explained. Herein, we first describe the establishment of a population pharmacokinetic model of cefaclor for healthy Koreans that might be useful for customizing cefaclor or exploring additional covariates in patients. Full article

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16 pages, 2345 KiB

Open AccessArticle

Effect of Application Amounts on In Vitro Dermal Absorption Test Using Caffeine and Testosterone

by Jueng-Eun Im, Hyang Yeon Kim, Jung Dae Lee, Jin-Ju Park, Kyung-Soo Kang and Kyu-Bong Kim

Pharmaceutics 2021, 13(5), 641; https://doi.org/10.3390/pharmaceutics13050641 - 30 Apr 2021

Cited by 12 | Viewed by 3565

Abstract

Dermal absorption of chemicals is a key factor in risk assessment. This study investigated the effects of different amounts of application on dermal absorption and suggested an appropriate application dose for proper dermal absorption. Caffeine and testosterone were chosen as test compounds. An [...] Read more.

Dermal absorption of chemicals is a key factor in risk assessment. This study investigated the effects of different amounts of application on dermal absorption and suggested an appropriate application dose for proper dermal absorption. Caffeine and testosterone were chosen as test compounds. An in vitro dermal absorption test was performed using a Franz diffusion cell. Different amounts (5, 10, 25, and 50 mg (or µL)/cm²) of semisolid (cream) and liquid (solution) formulations containing 1% caffeine and 0.1% testosterone were applied to rat and minipig (Micropig^®) skins. After 24 h, the concentrations of both compounds remaining on the skin surface and in the stratum corneum, dermis and epidermis, and receptor fluid were determined using LC-MS / MS or HPLC. Dermal absorption of both compounds decreased with increasing amounts of application in both skin types (rat and minipig) and formulations (cream and solution). Especially, dermal absorptions (%) of both compounds at 50 mg (or µL)/cm² was significantly lower compared to 5 or 10 mg (or µL)/cm² in both rat and minipig skins. Therefore, a low dose (5 or 10 mg (or µL)/cm²) of the formulation should be applied to obtain conservative dermal absorption. Full article

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14 pages, 3709 KiB

Open AccessArticle

BSA-Silver Nanoparticles: A Potential Multimodal Therapeutics for Conventional and Photothermal Treatment of Skin Cancer

by Dasom Kim, Reeju Amatya, Seungmi Hwang, Sumi Lee, Kyoung Ah Min and Meong Cheol Shin

Pharmaceutics 2021, 13(4), 575; https://doi.org/10.3390/pharmaceutics13040575 - 17 Apr 2021

Cited by 49 | Viewed by 4369

Abstract

Silver nanoparticles (NPs) have attracted a considerable interest in the field of cancer research due to their potential utility in cancer therapy. In the present study, we developed bovine serum albumin (BSA)-coated silver NPs (BSA-Silver NPs) and characterized in vitro multimodal therapeutic activities [...] Read more.

Silver nanoparticles (NPs) have attracted a considerable interest in the field of cancer research due to their potential utility in cancer therapy. In the present study, we developed bovine serum albumin (BSA)-coated silver NPs (BSA-Silver NPs) and characterized in vitro multimodal therapeutic activities of NPs for the treatment of skin cancer. BSA-Silver NPs were synthesized by a single-step reduction process, and the successful preparation was verified through a list of physical characterizations, including transmission electron microscopy (TEM), ultraviolet-visible (UV–VIS) light spectroscopy, dynamic light scattering (DLS), and Fourier transform infrared (FT-IR) spectroscopy. The synthesized BSA-Silver NPs showed marked cytocidal effects on B16F10 melanoma cells, which was likely caused by oxidative stress. BSA-Silver NPs also elicited significant anti-angiogenic effects on HUVEC (human umbilical vein endothelial cell) by inhibiting their proliferation, migration, and tube formation. Moreover, BSA-Silver NPs showed a considerable light-to-heat conversion ability, suggesting their utility as photothermal agents. Overall, our findings suggest that BSA-Silver NPs may be promising candidates for the multimodal therapy of skin cancer. Full article

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38 pages, 1528 KiB

Open AccessReview

Curcumin and Its Modified Formulations on Inflammatory Bowel Disease (IBD): The Story So Far and Future Outlook

by Adhimoolam Karthikeyan, Kim Na Young, Mohammad Moniruzzaman, Anteneh Marelign Beyene, Kyoungtag Do, Senthil Kalaiselvi and Taesun Min

Pharmaceutics 2021, 13(4), 484; https://doi.org/10.3390/pharmaceutics13040484 - 2 Apr 2021

Cited by 59 | Viewed by 8851

Abstract

Inflammatory bowel disease (IBD) is a chronic relapsing and remitting inflammatory disorder of the small intestine and colon. IBD includes ulcerative colitis (UC) and Crohn’s disease (CD), and it is a major factor for the development of colon cancer, referred to as colitis-associated [...] Read more.

Inflammatory bowel disease (IBD) is a chronic relapsing and remitting inflammatory disorder of the small intestine and colon. IBD includes ulcerative colitis (UC) and Crohn’s disease (CD), and it is a major factor for the development of colon cancer, referred to as colitis-associated cancer (CAC). The current treatment of IBD mainly includes the use of synthetic drugs and monoclonal antibodies. However, these drugs have side effects over long-term use, and the high relapse rate restricts their application. In the recent past, many studies had witnessed a surge in applying plant-derived products to manage various diseases, including IBD. Curcumin is a bioactive component derived from a rhizome of turmeric (Curcuma longa). Numerous in vitro and in vivo studies show that curcumin may interact with many cellular targets (NF-κB, JAKs/STATs, MAPKs, TNF-γ, IL-6, PPARγ, and TRPV1) and effectively reduce the progression of IBD with promising results. Thus, curcumin is a potential therapeutic agent for patients with IBD once it significantly decreases clinical relapse in patients with quiescent IBD. This review aims to summarize recent advances and provide a comprehensive picture of curcumin’s effectiveness in IBD and offer our view on future research on curcumin in IBD treatment. Full article

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17 pages, 1462 KiB

Open AccessArticle

Pharmacokinetic Changes According to Single or Multiple Oral Administrations of Socheongryong-Tang to Rats: Presented as a Typical Example of Changes in the Pharmacokinetics Following Multiple Exposures to Herbal Medicines

by Seung-Hyun Jeong, Ji-Hun Jang, Da-Hwa Jung, Guk-Yeo Lee and Yong-Bok Lee

Pharmaceutics 2021, 13(4), 478; https://doi.org/10.3390/pharmaceutics13040478 - 1 Apr 2021

Cited by 4 | Viewed by 2799

Abstract

The purpose of this study was to investigate the pharmacokinetic properties of ephedrine, paeoniflorin, and cinnamic acid after single or multiple doses of Socheongryong-tang (SCRT) were administered to rats, and to present an example of the pharmacokinetic changes following multiple doses of an [...] Read more.

The purpose of this study was to investigate the pharmacokinetic properties of ephedrine, paeoniflorin, and cinnamic acid after single or multiple doses of Socheongryong-tang (SCRT) were administered to rats, and to present an example of the pharmacokinetic changes following multiple doses of an herbal medicine. SCRT is a traditional herbal medicine that has been used clinically for a long time, and its main ingredients include ephedrine, paeoniflorin, and cinnamic acid. However, studies on the pharmacokinetic properties of SCRT are insufficient, and particularly, no pharmacokinetic information has been reported for multiple doses. In this study, SCRT was administered orally to rats once or multiple times, and plasma sampled at different times was quantitatively analyzed for ephedrine, paeoniflorin, and cinnamic acid using ultra-high-performance liquid chromatography-tandem mass spectrometry. There was a difference between the pharmacokinetic parameter values of each component (especially in paeoniflorin and cinnamic acid) obtained after single or multiple doses of SCRT. The actual observed values of each component obtained after multiple doses of SCRT were clearly different from the predicted results of multiple-dose simulations based on the pharmacokinetic profiles obtained after a single dose. The results confirmed that the plasma concentrations and, thus, exposures to paeoniflorin and cinnamic acid were significantly increased when SCRT was administered multiple times, whereas that of ephedrine was not. The results of this study are expected to provide useful pharmacokinetic data for the safety and efficacy evaluation of SCRT in the future and demonstrate the necessity of pharmacokinetic comparison studies according to single or multiple oral administrations of herbal medicines. Full article

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16 pages, 3432 KiB

Open AccessArticle

Synergistic Effect of Growth Factor Releasing Polymeric Nanoparticles and Ultrasound Stimulation on Osteogenic Differentiation

by Minki Jin, Bo Seok Kim, Sung Ho Seo, Minjeong Kim, Yun Gyeong Kang, Jung-Woog Shin, Kwan Hyung Cho, Meong Cheol Shin, Changhan Yoon and Kyoung Ah Min

Pharmaceutics 2021, 13(4), 457; https://doi.org/10.3390/pharmaceutics13040457 - 27 Mar 2021

Cited by 6 | Viewed by 2634

Abstract

Mesenchymal stem cells (MSCs) have been extensively used in the tissue regeneration therapy. Ex vivo therapy with well-differentiated osteogenic cells is known as an efficient treatment for musculoskeletal diseases, including rheumatoid diseases. However, along with its high cost, the current therapy has limitations [...] Read more.

Mesenchymal stem cells (MSCs) have been extensively used in the tissue regeneration therapy. Ex vivo therapy with well-differentiated osteogenic cells is known as an efficient treatment for musculoskeletal diseases, including rheumatoid diseases. However, along with its high cost, the current therapy has limitations in terms of restoring bone regeneration procedures. An efficient process for the cell differentiation to obtain a large number of functionalized osteogenic cells is necessary. Therefore, it is strongly recommended to develop strategies to produce sufficient numbers of well-differentiated osteogenic cells from the MSCs. In general, differentiation media with growth factors have been used to facilitate cell differentiation. In the present study, the poly (lactic-co-glycolic acid) (PLGA) nanoparticles incorporating the growth factors were included in the media, resulting in releasing growth factors (dexamethasone and β-glycerophosphate) in the media in the controlled manner. Stable growth and early differentiation of osteogenic cells were achieved by the PLGA-based growth factor releasing system. Moreover, low intensity pulsed ultrasound was applied to this system to induce cell differentiation process. The results revealed that, as a biomarker at early stage of osteogenic cell differentiation, Lamin A/C nuclear protein was efficiently expressed in the cells growing in the presence of PLGA-based growth factor reservoirs and ultrasound. In conclusion, our results showed that the ultrasound stimulation combined with polymeric nanoparticles releasing growth factors could potentially induce osteogenic cell differentiation. Full article

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20 pages, 4064 KiB

Open AccessArticle

Antifungal Activity of 1,4-Dialkoxynaphthalen-2-Acyl Imidazolium Salts by Inducing Apoptosis of Pathogenic Candida spp.

by Jisue Lee, Jae-Goo Kim, Haena Lee, Tae Hoon Lee, Ki-Young Kim and Hakwon Kim

Pharmaceutics 2021, 13(3), 312; https://doi.org/10.3390/pharmaceutics13030312 - 27 Feb 2021

Cited by 9 | Viewed by 2918

Abstract

Even though Candida spp. are staying commonly on human skin, it is also an opportunistic pathogenic fungus that can cause candidiasis. The emergence of resistant Candida strains and the toxicity of antifungal agents have encouraged the development of new classes of potent antifungal [...] Read more.

Even though Candida spp. are staying commonly on human skin, it is also an opportunistic pathogenic fungus that can cause candidiasis. The emergence of resistant Candida strains and the toxicity of antifungal agents have encouraged the development of new classes of potent antifungal agents. Novel naphthalen-2-acyl imidazolium salts (NAIMSs), especially 1,4-dialkoxy-NAIMS from 1,4-dihydroxynaphthalene, were prepared and evaluated for antifungal activity. Those derivatives showed prominent anti-Candida activity with a minimum inhibitory concentration (MIC) of 3.125 to 6.26 μg/mL in 24 h based on microdilution antifungal susceptibility test. Among the tested compounds, NAIMS 7c showed strongest antifungal activity with 3.125 μg/mL MIC value compared with miconazole which showed 12.5 μg/mL MIC value against Candida spp., and more importantly >100 μg/mL MIC value against C. auris. The production of reactive oxygen species (ROS) was increased and JC-1 staining showed the loss of mitochondrial membrane potential in C. albicans by treatment with NAIMS 7c. The increased release of ultraviolet (UV) absorbing materials suggested that NAIMS 7c could cause cell busting. The expression of apoptosis-related genes was induced in C. albicans by NAIMS 7c treatment. Taken together, the synthetic NAIMSs are of high interest as novel antifungal agents given further in vivo examination. Full article

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10 pages, 2424 KiB

Open AccessArticle

Enhanced Stability of Indocyanine Green by Encapsulation in Zein-Phosphatidylcholine Hybrid Nanoparticles for Use in the Phototherapy of Cancer

by Eun-Hye Lee, Mi-Kyung Lee and Soo-Jeong Lim

Pharmaceutics 2021, 13(3), 305; https://doi.org/10.3390/pharmaceutics13030305 - 26 Feb 2021

Cited by 27 | Viewed by 2919

Abstract

Indocyanine green (ICG) is a clinically approved near-infrared dye that has shown promise as a photosensitizer for the phototherapy of cancer. However, its chemical instability in an aqueous solution has limited its clinical application. Encapsulating ICG in liposomes, phosphatidylcholine nanoparticles (PC-NP), has shown [...] Read more.

Indocyanine green (ICG) is a clinically approved near-infrared dye that has shown promise as a photosensitizer for the phototherapy of cancer. However, its chemical instability in an aqueous solution has limited its clinical application. Encapsulating ICG in liposomes, phosphatidylcholine nanoparticles (PC-NP), has shown partial effectiveness in stabilizing it. Prompted by our recent finding that the zein-phosphatidylcholine hybrid nanoparticles (Z/PC-NP) provide an advanced drug carrier compared to PC-NP, we herein investigated the potential of Z/PC-NP as an improved ICG formulation. Dynamic light scattering analysis, transmission electron microscopy, and Fourier-transform infrared spectroscopy studies showed that ICG was encapsulated in Z/PC-NP without hampering the high colloidal stability of the Z/PC-NP. During storage, the Z/PC-NP almost completely inhibited the ICG aggregation, whereas the PC-NP did so partially. The Z/PC-NP also more effectively blocked the ICG degradation compared to the PC-NP. The phototoxicity of ICG encapsulated in Z/PC-NP on cancer cells was twofold higher than that in the PC-NP. The ICG encapsulated in Z/PC-NP, but not in PC-NP, maintained its photocytotoxicity after four-day storage. These findings highlight the promising potential of Z/PC-NP as an ICG formulation that provides a higher stabilization effect than PC-NP. Full article

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25 pages, 5378 KiB

Open AccessArticle

Quality by Design Applied Development of Immediate-Release Rabeprazole Sodium Dry-Coated Tablet

by Sang-Ho Lee and Joo-Eun Kim

Pharmaceutics 2021, 13(2), 259; https://doi.org/10.3390/pharmaceutics13020259 - 14 Feb 2021

Cited by 15 | Viewed by 8072

Abstract

The aim of this study was to develop immediate-release oral rabeprazole sodium tablets with rapid efficacy and gastric stability for the treatment of gastroesophageal reflux disease. Rabeprazole sodium is a commonly prescribed proton pump inhibitor; however, it is extremely unstable and degrades in [...] Read more.

The aim of this study was to develop immediate-release oral rabeprazole sodium tablets with rapid efficacy and gastric stability for the treatment of gastroesophageal reflux disease. Rabeprazole sodium is a commonly prescribed proton pump inhibitor; however, it is extremely unstable and degrades in acidic environments. Hence, it has been manufactured and supplied only in enteric-coated tablet form, while immediate-release (IR) formulations for this drug are very limited. In this study, we applied the quality by design (QbD) approach to formulate and optimize an IR dry-coated tablet containing rabeprazole sodium as an inner core with an outer sodium bicarbonate layer to stabilize the active pharmaceutical ingredient at gastric pH. We also investigated the stability of the pharmaceutical dosage form and its pharmacokinetic profile. The results show that the developed tablets are stable for approximately 12 months and have a high dissolution rate, greater than or equal to 90% at 30 min. Further, in vivo beagle pharmacokinetics confirmed that the newly developed IR tablet had an AUC_t which is bioequivalent to the existing delayed-release rabeprazole tablet; however, its T_max was 0.5 h, which is up to seven times faster than that of the existing tablet. Moreover, the IR tablet was found to immediately absorb in the stomach. Hence, the development of IR tablets can be used as a platform to overcome the technical and commercial limitations currently associated with various proton pump inhibitors used to treat patients with gastroesophageal reflux disease that require immediate therapeutic relief. Full article

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16 pages, 3041 KiB

Open AccessArticle

Evaluation of Lidocaine and Metabolite Pharmacokinetics in Hyaluronic Acid Injection

by Ju Hee Kim, Dong Wook Kang, Go-Wun Choi, Sang Bok Lee, Seongjin Lee and Hea-Young Cho

Pharmaceutics 2021, 13(2), 203; https://doi.org/10.3390/pharmaceutics13020203 - 2 Feb 2021

Cited by 6 | Viewed by 4514

Abstract

Lidocaine-incorporated hyaluronic acid injection (LHA) is considered a promising way to increase patient compliance. Various reviews and analyses have been conducted to verify that the addition of lidocaine had no effect on the product quality of hyaluronic acid injections. However, possible pharmacokinetic (PK) [...] Read more.

Lidocaine-incorporated hyaluronic acid injection (LHA) is considered a promising way to increase patient compliance. Various reviews and analyses have been conducted to verify that the addition of lidocaine had no effect on the product quality of hyaluronic acid injections. However, possible pharmacokinetic (PK) alterations of lidocaine and its active metabolites, monoethylglycylxylidide (MEGX) and glycylxylidide (GX), in hyaluronic acid injection have not been studied so far. Thus, the objective of this study was to evaluate lidocaine and its metabolite PK after 0.3% lidocaine solution or LHA injection and to investigate any changes in PK profiles of lidocaine and its active metabolites. To do this, a novel bio-analytical method for simultaneous determination of lidocaine, MEGX, and GX in rat plasma was developed and validated. Then, plasma concentrations of lidocaine and its active metabolites MEGX and GX following subcutaneous (SC) injection of 0.3% lidocaine solution or LHA with 0.3–1% lidocaine in male Sprague-Dawley rats were successfully determined. The obtained data were used to develop a parent-metabolite pharmacokinetic (PK) model for LHA injection. The half-life, dose-normalized C_max, and AUC_inf of lidocaine after SC injection of lidocaine solution and LHA did not show statistically significant difference. The PK characteristics of lidocaine after LHA administration were best captured using a two-compartment model with combined first-order and transit absorption and its clearance described with Michaelis–Menten and first-order elimination kinetics. Two one-compartment models were consecutively added to the parent model for the metabolites. In conclusion, the incorporation of lidocaine in hyaluronic acid filler injection did not alter the chemical’s pharmacokinetic characteristics. Full article

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18 pages, 8802 KiB

Open AccessArticle

Optimization of Mesoporous Silica Nanoparticles through Statistical Design of Experiment and the Application for the Anticancer Drug

by Min-Ki Kim, Do-Hyung Ki, Young-Guk Na, Hae-Soo Lee, Jong-Suep Baek, Jae-Young Lee, Hong-Ki Lee and Cheong-Weon Cho

Pharmaceutics 2021, 13(2), 184; https://doi.org/10.3390/pharmaceutics13020184 - 31 Jan 2021

Cited by 45 | Viewed by 5932

Abstract

The synthesis process or composition of mesoporous silica nanoparticles (MSNs) affects the physicochemical properties. Using these properties, MSNs were synthesized through the Box–Behnken design (BBD) among statistical experimental methods. The effect of the amounts of synthetic reagents, hexadecyl triethyl ammonium bromide (CTAB), tetraethyl [...] Read more.

The synthesis process or composition of mesoporous silica nanoparticles (MSNs) affects the physicochemical properties. Using these properties, MSNs were synthesized through the Box–Behnken design (BBD) among statistical experimental methods. The effect of the amounts of synthetic reagents, hexadecyl triethyl ammonium bromide (CTAB), tetraethyl orthosilicate (TEOS), and 2 N sodium hydroxide (NaOH), was studied using the reaction surface design. Surface area, particle size, and zeta potential were set as response values. The physicochemical properties of the optimized MSNs were evaluated, and the effect as a drug delivery system was evaluated by loading doxorubicin hydrochloride (DOX). Nano-sized MSNs were successfully prepared with 0.617 g of CTAB, 8.417 mL of TEOS, and 2.726 mL of 2 N NaOH and showed excellent physicochemical properties. The optimized MSNs showed negligible toxicity in MCF-7 cells. The drug release profile from DOX-loaded MSNs (MSN@DOX) showed an increased rate of release with decreasing pH of the medium, with the release profile sustained for 48 h. In the cytotoxicity test, the sustained drug release mechanism of MSN@DOX was confirmed. This study proposed a new statistical approach to the synthesis of MSNs. Full article

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16 pages, 2981 KiB

Open AccessArticle

Hyaluronidase Inhibitor-Incorporated Cross-Linked Hyaluronic Acid Hydrogels for Subcutaneous Injection

by Min-Hwan Kim, Ju-Hwan Park, Duy-Thuc Nguyen, Sungyun Kim, Da In Jeong, Hyun-Jong Cho and Dae-Duk Kim

Pharmaceutics 2021, 13(2), 170; https://doi.org/10.3390/pharmaceutics13020170 - 27 Jan 2021

Cited by 19 | Viewed by 4931

Abstract

Hyaluronidase (HAase) inhibitor-incorporated hyaluronic acid (HA) hydrogel cross-linked with 1,4-butanediol diglycidyl ether (BDDE) was designed to reduce the toxicity risk induced by BDDE and its biodegradation rate in subcutaneous tissue. The formulation composition of hydrogel and its preparation method were optimized to have [...] Read more.

Hyaluronidase (HAase) inhibitor-incorporated hyaluronic acid (HA) hydrogel cross-linked with 1,4-butanediol diglycidyl ether (BDDE) was designed to reduce the toxicity risk induced by BDDE and its biodegradation rate in subcutaneous tissue. The formulation composition of hydrogel and its preparation method were optimized to have a high swelling ratio and drug content. Quercetin (QCT) and quetiapine (QTP), as an HAase inhibitor and model drug, respectively, were incorporated into the cross-linked hydrogel using the antisolvent precipitation method for extending their release after subcutaneous injection. The cross-linked HA (cHA)-based hydrogels displayed appropriate viscoelasticity and injectability for subcutaneous injection. The incorporation of QCT (as an HAase inhibitor) in the cHA hydrogel formulation resulted in slower in vitro and in vivo degradation profiles compared to the hydrogel without QCT. Single dosing of optimized hydrogel injected via a subcutaneous route in rats did not induce any acute toxicities in the blood chemistry and histological staining studies. In the pharmacokinetic study of rats following subcutaneous injection, the cHA hydrogel with QCT exhibited a lower maximum QTP concentration and longer half-life and mean residence time values compared to the hydrogel without QCT. All of these results support the designed HAase inhibitor-incorporated cHA hydrogel being a biocompatible subcutaneous injection formulation for sustained drug delivery. Full article

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20 pages, 2621 KiB

Open AccessArticle

Nanoporous Silica Entrapped Lipid-Drug Complexes for the Solubilization and Absorption Enhancement of Poorly Soluble Drugs

by Hey-Won Shin, Joo-Eun Kim and Young-Joon Park

Pharmaceutics 2021, 13(1), 63; https://doi.org/10.3390/pharmaceutics13010063 - 6 Jan 2021

Cited by 9 | Viewed by 3705

Abstract

This study aims to examine the contribution of nanoporous silica entrapped lipid-drug complexes (NSCs) in improving the solubility and bioavailability of dutasteride (DUT). An NSC was loaded with DUT (dissolved in lipids) and dispersed at a nanoscale level using an entrapment technique. NSC [...] Read more.

This study aims to examine the contribution of nanoporous silica entrapped lipid-drug complexes (NSCs) in improving the solubility and bioavailability of dutasteride (DUT). An NSC was loaded with DUT (dissolved in lipids) and dispersed at a nanoscale level using an entrapment technique. NSC microemulsion formation was confirmed using a ternary phase diagram, while the presence of DUT and lipid entrapment in NSC was confirmed using scanning electron microscopy. Differential scanning calorimetry and X-ray diffraction revealed the amorphous properties of NSC. The prepared all NSC had excellent flowability and enhanced DUT solubility but showed no significant difference in drug content homogeneity. An increase in the lipid content of NSC led to an increase in the DUT solubility. Further the NSC were formulated as tablets using D-α tocopheryl polyethylene glycol 1000 succinate, glyceryl caprylate/caprate, and Neusilin^®. The NSC tablets showed a high dissolution rate of 99.6% at 30 min. Furthermore, NSC stored for 4 weeks at 60 °C was stable during dissolution testing. Pharmacokinetic studies performed in beagle dogs revealed enhanced DUT bioavailability when administered as NSC tablets. NSC can be used as a platform to develop methods to overcome the technical and commercial limitations of lipid-based preparations of poorly soluble drugs. Full article

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2020

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37 pages, 3173 KiB

Open AccessReview

Potential and Applications of Nanocarriers for Efficient Delivery of Biopharmaceuticals

by Alam Zeb, Isra Rana, Ho-Ik Choi, Cheol-Ho Lee, Seong-Woong Baek, Chang-Wan Lim, Namrah Khan, Sadia Tabassam Arif, Najam us Sahar, Arooj Mohsin Alvi, Fawad Ali Shah, Fakhar ud Din, Ok-Nam Bae, Jeong-Sook Park and Jin-Ki Kim

Pharmaceutics 2020, 12(12), 1184; https://doi.org/10.3390/pharmaceutics12121184 - 6 Dec 2020

Cited by 60 | Viewed by 7248

Abstract

During the past two decades, the clinical use of biopharmaceutical products has markedly increased because of their obvious advantages over conventional small-molecule drug products. These advantages include better specificity, potency, targeting abilities, and reduced side effects. Despite the substantial clinical and commercial success, [...] Read more.

During the past two decades, the clinical use of biopharmaceutical products has markedly increased because of their obvious advantages over conventional small-molecule drug products. These advantages include better specificity, potency, targeting abilities, and reduced side effects. Despite the substantial clinical and commercial success, the macromolecular structure and intrinsic instability of biopharmaceuticals make their formulation and administration challenging and render parenteral delivery as the only viable option in most cases. The use of nanocarriers for efficient delivery of biopharmaceuticals is essential due to their practical benefits such as protecting from degradation in a hostile physiological environment, enhancing plasma half-life and retention time, facilitating absorption through the epithelium, providing site-specific delivery, and improving access to intracellular targets. In the current review, we highlight the clinical and commercial success of biopharmaceuticals and the overall applications and potential of nanocarriers in biopharmaceuticals delivery. Effective applications of nanocarriers for biopharmaceuticals delivery via invasive and noninvasive routes (oral, pulmonary, nasal, and skin) are presented here. The presented data undoubtedly demonstrate the great potential of combining nanocarriers with biopharmaceuticals to improve healthcare products in the future clinical landscape. In conclusion, nanocarriers are promising delivery tool for the hormones, cytokines, nucleic acids, vaccines, antibodies, enzymes, and gene- and cell-based therapeutics for the treatment of multiple pathological conditions. Full article

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17 pages, 13902 KiB

Open AccessArticle

Highly Red Light-Emitting Erbium- and Lutetium-Doped Core-Shell Upconverting Nanoparticles Surface-Modified with PEG-Folic Acid/TCPP for Suppressing Cervical Cancer HeLa Cells

by Kyungseop Lim, Hwang Kyung Kim, Xuan Thien Le, Nguyen Thi Nguyen, Eun Seong Lee, Kyung Taek Oh, Han-Gon Choi and Yu Seok Youn

Pharmaceutics 2020, 12(11), 1102; https://doi.org/10.3390/pharmaceutics12111102 - 17 Nov 2020

Cited by 16 | Viewed by 4522

Abstract

Photodynamic therapy (PDT) combined with upconverting nanoparticles (UCNPs) are viewed together as an effective method of ablating tumors. After absorbing highly tissue-penetrating near-infrared (NIR) light, UCNPs emit a shorter wavelength light (~660 nm) suitable for PDT. In this study, we designed and prepared [...] Read more.

Photodynamic therapy (PDT) combined with upconverting nanoparticles (UCNPs) are viewed together as an effective method of ablating tumors. After absorbing highly tissue-penetrating near-infrared (NIR) light, UCNPs emit a shorter wavelength light (~660 nm) suitable for PDT. In this study, we designed and prepared highly red fluorescence-emitting silica-coated core-shell upconverting nanoparticles modified with polyethylene glycol (PEG_5k)-folic acid and tetrakis(4-carboxyphenyl)porphyrin (TCPP) (UCNPs@SiO₂-NH₂@FA/PEG/TCPP) as an efficient photodynamic agent for killing tumor cells. The UCNPs consisted of two simple lanthanides, erbium and lutetium, as the core and shell, respectively. The unique core-shell combination enabled the UCNPs to emit red light without green light. TCPP, folic acid, and PEG were conjugated to the outer silica layer of UCNPs as a photosensitizing agent, a ligand for tumor attachment, and a dispersing stabilizer, respectively. The prepared UCNPs of ~50 nm diameter and −34.5 mV surface potential absorbed 808 nm light and emitted ~660 nm red light. Most notably, these UCNPs were physically well dispersed and stable in the aqueous phase due to PEG attachment and were able to generate singlet oxygen (¹O₂) with a high efficacy. The HeLa cells were treated with each UCNP sample (0, 1, 5, 10, 20, 30 μg/mL as a free TCPP). The results showed that the combination of UCNPs@SiO₂-NH₂@FA/PEG/TCPP and the 808 nm laser was significantly cytotoxic to HeLa cells, almost to the same degree as naïve TCPP plus the 660 nm laser based on MTT and Live/Dead assays. Furthermore, the UCNPs@SiO₂-NH₂@FA/PEG/TCPP was well internalized into HeLa cells and three-dimensional HeLa spheroids, presumably due to the surface folic acid and small size in conjunction with endocytosis and the nonspecific uptake. We believe that our UCNPs@SiO₂-NH₂@FA/PEG/TCPP will serve as a new platform for highly efficient and deep-penetrating photodynamic agents suitable for various tumor treatments. Full article

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15 pages, 3018 KiB

Open AccessArticle

Bioavailability of the Common Cold Medicines in Jellies for Oral Administration

by Ki Hyun Kim, Minju Jun and Mi-Kyung Lee

Pharmaceutics 2020, 12(11), 1073; https://doi.org/10.3390/pharmaceutics12111073 - 10 Nov 2020

Cited by 14 | Viewed by 6473

Abstract

Jellies for oral administration have been suggested as alternative dosage forms to conventional tablets for improved palatability and compliances for pediatric and geriatric patients. To evaluate the effect of jelly formulation on the bioavailability of cold medicines, two types of jellies were prepared [...] Read more.

Jellies for oral administration have been suggested as alternative dosage forms to conventional tablets for improved palatability and compliances for pediatric and geriatric patients. To evaluate the effect of jelly formulation on the bioavailability of cold medicines, two types of jellies were prepared for a fixed-dose combination of acetaminophen (AAP), chlorpheniramine maleate (CPM), dextromethorphan hydrobromide (DMH), and dl-methylephedrine hydrochloride (MEH). Jelly-S and Jelly-H were fabricated using carrageenan and locust bean gum in the absence and presence of xanthan gum, respectively. In vitro dissolution and in vivo absorption of the four drugs in the jellies were compared with other conventional formulations, a syrup and two types of immediate-release (IR) tablets with different hardness, Tablet-S (15 kPa) and Tablet-H (20 kPa). All the formulations exhibited more than 80% dissolution rate within 2 h even though the syrup, Jelly-S, and Tablet-S showed higher 30-min dissolution compared to Jelly-H and Tablet-H. The dissolution rates from the jellies decreased with increasing pH, which resulted in the slowest dissolution in pH 6.8 compared to the syrup and IR tablets. When administered orally to beagle dogs, all five formulations were determined not to be bioequivalent. However, Jelly-S and Jelly-H showed 0.82–1.05 of the geometric mean ratios (GMRs) of AUC_0-t for all four drugs compared to the syrup suggesting comparable absorption. In two IR tablets, GMRs of AUC_0-t were in a range of 0.55–0.95 indicating a tendency of lower absorption than the syrup and jellies. In conclusion, jelly can be a patient-centered formulation with comparable bioavailability to syrup. Full article

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14 pages, 2425 KiB

Open AccessArticle

An On-Demand pH-Sensitive Nanocluster for Cancer Treatment by Combining Photothermal Therapy and Chemotherapy

by Taehoon Sim, Chaemin Lim, Ngoc Ha Hoang, Yuseon Shin, Jae Chang Kim, June Yong Park, Jaewon Her, Eun Seong Lee, Yu Seok Youn and Kyung Taek Oh

Pharmaceutics 2020, 12(9), 839; https://doi.org/10.3390/pharmaceutics12090839 - 2 Sep 2020

Cited by 10 | Viewed by 4015

Abstract

Combination therapy is considered to be a promising strategy for improving the therapeutic efficiency of cancer treatment. In this study, an on-demand pH-sensitive nanocluster (NC) system was prepared by the encapsulation of gold nanorods (AuNR) and doxorubicin (DOX) by a pH-sensitive polymer, poly(aspartic [...] Read more.

Combination therapy is considered to be a promising strategy for improving the therapeutic efficiency of cancer treatment. In this study, an on-demand pH-sensitive nanocluster (NC) system was prepared by the encapsulation of gold nanorods (AuNR) and doxorubicin (DOX) by a pH-sensitive polymer, poly(aspartic acid-graft-imidazole)-PEG, to enhance the therapeutic effect of chemotherapy and photothermal therapy. At pH 6.5, the NC systems formed aggregated structures and released higher drug amounts while sustaining a stable nano-assembly, structured with less systemic toxicity at pH 7.4. The NC could also increase antitumor efficacy as a result of improved accumulation and release of DOX from the NC system at pH_ex and pH_en with locally applied near-infrared light. Therefore, an NC system would be a potent strategy for on-demand combination treatment to target tumors with less systemic toxicity and an improved therapeutic effect. Full article

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