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Pharmaceutics, Volume 4, Issue 1 (March 2012) – 15 articles , Pages 1-251

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Research

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3710 KiB  
Article
Recrystallization of Commercial Carbamazepine Samples—A Strategy to Control Dissolution Variability
by Felicia Flicker, Veronika A. Eberle and Gabriele Betz
Pharmaceutics 2012, 4(1), 58-70; https://doi.org/10.3390/pharmaceutics4010058 - 13 Jan 2012
Cited by 7 | Viewed by 9902
Abstract
Physical properties of commercial carbamazepine (CBZ) samples can significantly influence drug release and thereby jeopardize bioequivalence of the final dosage form. The aim of this study was to reduce variability in commercial CBZ samples by recrystallization. CBZ samples of four different suppliers were [...] Read more.
Physical properties of commercial carbamazepine (CBZ) samples can significantly influence drug release and thereby jeopardize bioequivalence of the final dosage form. The aim of this study was to reduce variability in commercial CBZ samples by recrystallization. CBZ samples of four different suppliers were recrystallized in ethanol solution containing 1% polyvinylpyrrolidone (PVP). CBZ samples were analyzed by disk intrinsic dissolution rate (DIDR), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Recrystallized CBZ samples showed strongly reduced variability in DIDR compared to the untreated CBZ samples. Moreover, transformation process to CBZ dihydrate was inhibited; no dihydrate crystals were visible on compact surfaces after 8 h intrinsic dissolution measurement. Recrystallized CBZ samples showed no change in polymorphic form, however, particle size and shape was inhomogenous. In binary mixtures with microcrystalline cellulose, recrystallized CBZ samples again showed difference in drug release. This difference was associated with the inhomogenous particle size in the recrystallized CBZ samples. The results show that a controlled grinding step is required after recrystallization. We suggest the recrystallization in presence of 1% PVP followed by a controlled grinding step as a strategy to reduce dissolution variability in commercial CBZ samples. Full article
(This article belongs to the Special Issue Solid Dosage Forms)
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295 KiB  
Article
Atomic Pairwise Distribution Function Analysis of the Amorphous Phase Prepared by Different Manufacturing Routes
by Johan P. Boetker, Vishal Koradia, Thomas Rades, Jukka Rantanen and Marja Savolainen
Pharmaceutics 2012, 4(1), 93-103; https://doi.org/10.3390/pharmaceutics4010093 - 31 Jan 2012
Cited by 13 | Viewed by 7420
Abstract
Amlodipine besilate, a calcium channel antagonist, exists in several solid forms. Processing of anhydrate and dihydrate forms of this drug may lead to solid state changes, and is therefore the focus of this study. Milling was performed for the anhydrate form, whereas the [...] Read more.
Amlodipine besilate, a calcium channel antagonist, exists in several solid forms. Processing of anhydrate and dihydrate forms of this drug may lead to solid state changes, and is therefore the focus of this study. Milling was performed for the anhydrate form, whereas the dihydrate form was subjected to quench cooling thereby creating an amorphous form of the drug from both starting materials. The milled and quench cooled samples were, together with the crystalline starting materials, analyzed with X-ray powder diffraction (XRPD), Raman spectroscopy and atomic pair-wise distribution function (PDF) analysis of the XRPD pattern. When compared to XRPD and Raman spectroscopy, the PDF analysis was superior in displaying the difference between the amorphous samples prepared by milling and quench cooling approaches of the two starting materials. Full article
(This article belongs to the Special Issue The 1st Electronic Conference on Pharmaceutical Science)
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3218 KiB  
Article
Lecithin-Linker Microemulsion Gelatin Gels for Extended Drug Delivery
by Xiao-Yue Xuan, Yu-Ling Cheng and Edgar Acosta
Pharmaceutics 2012, 4(1), 104-129; https://doi.org/10.3390/pharmaceutics4010104 - 31 Jan 2012
Cited by 31 | Viewed by 11907
Abstract
This article introduces the formulation of alcohol-free, lecithin microemulsion-based gels (MBGs) prepared with gelatin as gelling agent. The influence of oil, water, lecithin and hydrophilic and lipophilic additives (linkers) on the rheological properties and appearance of these gels was systematically explored using ternary [...] Read more.
This article introduces the formulation of alcohol-free, lecithin microemulsion-based gels (MBGs) prepared with gelatin as gelling agent. The influence of oil, water, lecithin and hydrophilic and lipophilic additives (linkers) on the rheological properties and appearance of these gels was systematically explored using ternary phase diagrams. Clear MBGs were obtained in regions of single phase microemulsions (μEs) at room temperature. Increasing the water content in the formulation increased the elastic modulus of the gels, while increasing the oil content had the opposite effect. The hydrophilic additive (PEG-6-caprylic/capric glycerides) was shown to reduce the elastic modulus of gelatin gels, particularly at high temperatures. In contrast to anionic (AOT) μEs, the results suggest that in lecithin (nonionic) μEs, the introduction of gelatin “dehydrates” the μE. Finally, when the transdermal transport of lidocaine formulated in the parent μE and the resulting MBG were compared, only a minor retardation in the loading and release of lidocaine was observed. Full article
(This article belongs to the Special Issue Transdermal Drug Delivery)
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239 KiB  
Article
Probiotic Encapsulation Technology: From Microencapsulation to Release into the Gut
by Gildas K. Gbassi and Thierry Vandamme
Pharmaceutics 2012, 4(1), 149-163; https://doi.org/10.3390/pharmaceutics4010149 - 06 Feb 2012
Cited by 167 | Viewed by 16484
Abstract
Probiotic encapsulation technology (PET) has the potential to protect microorgansisms and to deliver them into the gut. Because of the promising preclinical and clinical results, probiotics have been incorporated into a range of products. However, there are still many challenges to overcome with [...] Read more.
Probiotic encapsulation technology (PET) has the potential to protect microorgansisms and to deliver them into the gut. Because of the promising preclinical and clinical results, probiotics have been incorporated into a range of products. However, there are still many challenges to overcome with respect to the microencapsulation process and the conditions prevailing in the gut. This paper reviews the methodological approach of probiotics encapsulation including biomaterials selection, choice of appropriate technology, in vitro release studies of encapsulated probiotics, and highlights the challenges to be overcome in this area. Full article
(This article belongs to the Special Issue Microencapsulation Technology Applied to Pharmaceutics)
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989 KiB  
Article
In Situ Focused Beam Reflectance Measurement (FBRM), Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) and Raman Characterization of the Polymorphic Transformation of Carbamazepine
by Yingying Zhao, Ying Bao, Jingkang Wang and Sohrab Rohani
Pharmaceutics 2012, 4(1), 164-178; https://doi.org/10.3390/pharmaceutics4010164 - 09 Feb 2012
Cited by 10 | Viewed by 9475
Abstract
The objective of this work was to study the polymorphic transformation of carbamazepine from Form II to Form III in 1-propanol during seeded isothermal batch crystallization. First, the pure Form II and Form III were obtained and characterized. Then their solubilities and metastable [...] Read more.
The objective of this work was to study the polymorphic transformation of carbamazepine from Form II to Form III in 1-propanol during seeded isothermal batch crystallization. First, the pure Form II and Form III were obtained and characterized. Then their solubilities and metastable zone limits were measured by in-situ attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and focused beam reflectance measurement (FBRM). A transition temperature at about 34.2 °C was deduced suggesting the enantiotropic nature of this compound over the studied temperature range. To quantify the polymorph ratio during the transformation process, a new in-situ quantitative method was developed to measure the fraction of Form II by Raman spectroscopy. Successful tracking of the nucleation of the stable form and the transformation from Form II to Form III during isothermal crystallization was achieved by Raman spectroscopy and FBRM. The results from these three in-situ techniques, FBRM, FTIR and Raman were consistent with each other. The results showed a strong dependency on the amount of seeds added during isothermal crystallization. Full article
(This article belongs to the Special Issue Solid Dosage Forms)
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330 KiB  
Article
Preparation and Characterization of Amino Acids-Based Trimethoprim Salts
by Amr ElShaer, Peter Hanson, Tony Worthington, Peter Lambert and Afzal R. Mohammed
Pharmaceutics 2012, 4(1), 179-196; https://doi.org/10.3390/pharmaceutics4010179 - 16 Feb 2012
Cited by 24 | Viewed by 8185
Abstract
Trimethoprim (TMP) is a dihydrofolate reductase (DHFR) inhibitor which prevents the conversion of dihydrofolic acid into tetrahydrofolic acid, resulting in the depletion of the latter and leading to bacterial death. Oral bioavailability of TMP is hindered by both its low solubility and low [...] Read more.
Trimethoprim (TMP) is a dihydrofolate reductase (DHFR) inhibitor which prevents the conversion of dihydrofolic acid into tetrahydrofolic acid, resulting in the depletion of the latter and leading to bacterial death. Oral bioavailability of TMP is hindered by both its low solubility and low permeability. This study aims to prepare novel salts of TMP using anionic amino acids; aspartic and glutamic acid as counter ions in order to improve solubility and dissolution. TMP salts were prepared by lyophilisation and characterized using FT-IR spectroscopy, proton nuclear magnetic resonance (1HNMR), Differential Scanning Calorimetry (DSC) and Thermogravimetric analysis (TGA). Both the amino acids formed salts with TMP in a 1:1 molar ratio and showed a 280 fold improvement in solubility. Investigation of the microbiological activity of the prepared salts against TMP sensitive Escherichia coli showed that the new salts not only retained antibacterial activity but also exhibited higher zone of inhibition which was attributed to improved physicochemical characters such as higher solubility and dissolution. The results are an important finding that could potentially impact on faster onset of antibacterial activity and reduced therapeutic dose when administered to patients. Studies are underway investigating the effect of ion-pairing TMP with amino acids on the permeability profile of the drug. Full article
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3246 KiB  
Article
Evaluation of Tissue Interactions with Mechanical Elements of a Transscleral Drug Delivery Device
by Sarah J. Cohen, Robison V. Paul Chan, Mark Keegan, Christopher M. Andreoli, Jeffrey T. Borenstein, Joan W. Miller and Evangelos S. Gragoudas
Pharmaceutics 2012, 4(1), 212-229; https://doi.org/10.3390/pharmaceutics4010212 - 12 Mar 2012
Cited by 2 | Viewed by 7098
Abstract
The goal of this work was to evaluate tissue-device interactions due to implantation of a mechanically operated drug delivery system onto the posterior sclera. Two test devices were designed and fabricated to model elements of the drug delivery device—one containing a free-spinning ball [...] Read more.
The goal of this work was to evaluate tissue-device interactions due to implantation of a mechanically operated drug delivery system onto the posterior sclera. Two test devices were designed and fabricated to model elements of the drug delivery device—one containing a free-spinning ball bearing and the other encasing two articulating gears. Openings in the base of test devices modeled ports for drug passage from device to sclera. Porous poly(tetrafluoroethylene) (PTFE) membranes were attached to half of the gear devices to minimize tissue ingrowth through these ports. Test devices were sutured onto rabbit eyes for 10 weeks. Tissue-device interactions were evaluated histologically and mechanically after removal to determine effects on device function and changes in surrounding tissue. Test devices were generally well-tolerated during residence in the animal. All devices encouraged fibrous tissue formation between the sclera and the device, fibrous tissue encapsulation and invasion around the device, and inflammation of the conjunctiva. Gear devices encouraged significantly greater inflammation in all cases and a larger rate of tissue ingrowth. PTFE membranes prevented tissue invasion through the covered drug ports, though tissue migrated in through other smaller openings. The torque required to turn the mechanical elements increased over 1000 times for gear devices, but only on the order of 100 times for membrane-covered gear devices and less than 100 times for ball bearing devices. Maintaining a lower device profile, minimizing microscale motion on the eye surface and covering drug ports with a porous membrane may minimize inflammation, decreasing the risk of damage to surrounding tissues and minimizing disruption of device operation. Full article
(This article belongs to the Special Issue Ocular Drug Delivery)
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Review

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7687 KiB  
Review
Trojan Microparticles for Drug Delivery
by Nicolas Anton, Anshuman Jakhmola and Thierry F. Vandamme
Pharmaceutics 2012, 4(1), 1-25; https://doi.org/10.3390/pharmaceutics4010001 - 06 Jan 2012
Cited by 51 | Viewed by 10668
Abstract
During the last decade, the US Food and Drug Administration (FDA) have regulated a wide range of products, (foods, cosmetics, drugs, devices, veterinary, and tobacco) which may utilize micro and nanotechnology or contain nanomaterials. Nanotechnology allows scientists to create, explore, and manipulate materials [...] Read more.
During the last decade, the US Food and Drug Administration (FDA) have regulated a wide range of products, (foods, cosmetics, drugs, devices, veterinary, and tobacco) which may utilize micro and nanotechnology or contain nanomaterials. Nanotechnology allows scientists to create, explore, and manipulate materials in nano-regime. Such materials have chemical, physical, and biological properties that are quite different from their bulk counterparts. For pharmaceutical applications and in order to improve their administration (oral, pulmonary and dermal), the nanocarriers can be spread into microparticles. These supramolecular associations can also modulate the kinetic releases of drugs entrapped in the nanoparticles. Different strategies to produce these hybrid particles and to optimize the release kinetics of encapsulated drugs are discussed in this review. Full article
(This article belongs to the Special Issue Microencapsulation Technology Applied to Pharmaceutics)
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414 KiB  
Review
Tissue Engineered Human Skin Equivalents
by Zheng Zhang and Bozena B. Michniak-Kohn
Pharmaceutics 2012, 4(1), 26-41; https://doi.org/10.3390/pharmaceutics4010026 - 06 Jan 2012
Cited by 123 | Viewed by 12664
Abstract
Human skin not only serves as an important barrier against the penetration of exogenous substances into the body, but also provides a potential avenue for the transport of functional active drugs/reagents/ingredients into the skin (topical delivery) and/or the body (transdermal delivery). In the [...] Read more.
Human skin not only serves as an important barrier against the penetration of exogenous substances into the body, but also provides a potential avenue for the transport of functional active drugs/reagents/ingredients into the skin (topical delivery) and/or the body (transdermal delivery). In the past three decades, research and development in human skin equivalents have advanced in parallel with those in tissue engineering and regenerative medicine. The human skin equivalents are used commercially as clinical skin substitutes and as models for permeation and toxicity screening. Several academic laboratories have developed their own human skin equivalent models and applied these models for studying skin permeation, corrosivity and irritation, compound toxicity, biochemistry, metabolism and cellular pharmacology. Various aspects of the state of the art of human skin equivalents are reviewed and discussed. Full article
(This article belongs to the Special Issue Transdermal Drug Delivery)
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759 KiB  
Review
Novel Experimental and Clinical Therapeutic Uses of Low-Molecular-Weight Heparin/Protamine Microparticles
by Satoko Kishimoto, Masayuki Ishihara, Megumi Takikawa, Yasutaka Mori, Hidemi Hattori, Masanori Fujita and Shingo Nakamura
Pharmaceutics 2012, 4(1), 42-57; https://doi.org/10.3390/pharmaceutics4010042 - 11 Jan 2012
Cited by 11 | Viewed by 7785
Abstract
Low-molecular-weight heparin/protamine microparticles (LMW-H/P MPs) were produced as a carrier for heparin-binding growth factors (GFs) and for various adhesive cells. A mixture of low-molecular-weight heparin (MW: approximately 5000 Da, 6.4 mg/mL) and protamine (MW: approximately 3000 Da, 10 mg/mL) at a ratio of [...] Read more.
Low-molecular-weight heparin/protamine microparticles (LMW-H/P MPs) were produced as a carrier for heparin-binding growth factors (GFs) and for various adhesive cells. A mixture of low-molecular-weight heparin (MW: approximately 5000 Da, 6.4 mg/mL) and protamine (MW: approximately 3000 Da, 10 mg/mL) at a ratio of 7:3 (vol:vol) yields a dispersion of microparticles (0.5–3 µm in diameter). LMW-H/P MPs immobilize, control the release and protect the activity of GFs. LMW-H/P MPs can also bind to cell surfaces, causing these cells to interact with the LMW-H/P MPs, inducing cells/MPs-aggregate formation and substantially promoting cellular viability. Furthermore, LMW-H/P MPs can efficiently bind to tissue culture plates and retain the binding of important GFs, such as fibroblast growth factor (FGF)-2. The LMW-H/P MPs-coated matrix with various GFs or cytokines may provide novel biomaterials that can control cellular activity such as growth and differentiation. Thus, LMW-H/P MPs are an excellent carrier for GFs and various cells and are an efficient coating matrix for cell cultures. Full article
(This article belongs to the Special Issue Microencapsulation Technology Applied to Pharmaceutics)
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928 KiB  
Review
Structure Enhancement Relationship of Chemical Penetration Enhancers in Drug Transport across the Stratum Corneum
by Doungdaw Chantasart and S. Kevin Li
Pharmaceutics 2012, 4(1), 71-92; https://doi.org/10.3390/pharmaceutics4010071 - 17 Jan 2012
Cited by 37 | Viewed by 8796 | Correction
Abstract
The stratum corneum is a major barrier of drug penetration across the skin in transdermal delivery. For effective transdermal drug delivery, skin penetration enhancers are used to overcome this barrier. In the past decades, a number of research studies were conducted to understand [...] Read more.
The stratum corneum is a major barrier of drug penetration across the skin in transdermal delivery. For effective transdermal drug delivery, skin penetration enhancers are used to overcome this barrier. In the past decades, a number of research studies were conducted to understand the mechanisms of skin penetration enhancers and to develop a structure enhancement relationship. Such understanding allows effective prediction of the effects of skin penetration enhancers, assists topical and transdermal formulation development, and avoids extensive enhancer screening in the transdermal delivery industry. In the past two decades, several hypotheses on chemical enhancer-induced penetration enhancement for transport across the skin lipoidal pathway have been examined based on a systematic approach. Particularly, a hypothesis that skin penetration enhancement is directly related to the concentration of the enhancers in the stratum corneum lipid domain was examined. A direct relationship between skin penetration enhancer potency (based on enhancer aqueous concentration in the diffusion cell chamber) and enhancer n-octanol-water partition coefficient was also established. The nature of the microenvironment of the enhancer site of action in the stratum corneum lipid domain was found to be mimicked by n-octanol. The present paper reviews the work related to these hypotheses and the relationships between skin penetration enhancement and enhancer concentration in the drug delivery media and stratum corneum lipids. Full article
(This article belongs to the Special Issue Transdermal Drug Delivery)
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1131 KiB  
Review
Polyamidoamine Dendrimer Conjugates with Cyclodextrins as Novel Carriers for DNA, shRNA and siRNA
by Hidetoshi Arima, Keiichi Motoyama and Taishi Higashi
Pharmaceutics 2012, 4(1), 130-148; https://doi.org/10.3390/pharmaceutics4010130 - 01 Feb 2012
Cited by 33 | Viewed by 8076
Abstract
Gene, short hairpin RNA (shRNA) and small interfering RNA (siRNA) delivery can be particularly used for the treatment of diseases by the entry of genetic materials mammalian cells either to express new proteins or to suppress the expression of proteins, respectively. Polyamidoamine (PAMAM) [...] Read more.
Gene, short hairpin RNA (shRNA) and small interfering RNA (siRNA) delivery can be particularly used for the treatment of diseases by the entry of genetic materials mammalian cells either to express new proteins or to suppress the expression of proteins, respectively. Polyamidoamine (PAMAM) StarburstTM dendrimers are used as non-viral vectors (carriers) for gene, shRNA and siRNA delivery. Recently, multifunctional PAMAM dendrimers can be used for the wide range of biomedical applications including intracellular delivery of genes and nucleic acid drugs. In this context, this review paper provides the recent findings on PAMAM dendrimer conjugates with cyclodextrins (CyDs) for gene, shRNA and siRNA delivery. Full article
(This article belongs to the Special Issue Gene Therapy)
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175 KiB  
Review
Ocular Drug Delivery for Glaucoma Management
by Nathan Gooch, Sarah A. Molokhia, Russell Condie, Randon Michael Burr, Bonnie Archer, Balamurali K. Ambati and Barbara Wirostko
Pharmaceutics 2012, 4(1), 197-211; https://doi.org/10.3390/pharmaceutics4010197 - 08 Mar 2012
Cited by 53 | Viewed by 9566
Abstract
Current glaucoma management modalities are hindered by low patient compliance and adherence. This can be due to highly complex treatment strategies or poor patient understanding. Treatments focus on the management or reduction of intraocular pressure. This is most commonly done through the use [...] Read more.
Current glaucoma management modalities are hindered by low patient compliance and adherence. This can be due to highly complex treatment strategies or poor patient understanding. Treatments focus on the management or reduction of intraocular pressure. This is most commonly done through the use of daily topical eye drops. Unfortunately, despite effective therapies, glaucoma continues to progress, possibly due to patients not adhering to their treatments. In order to mitigate these patient compliance issues, many sustained release treatments are being researched and are entering the clinic. Conjunctival, subconjunctival, and intravitreal inserts, punctal plugs, and drug depots are currently in clinical development. Each delivery system has hurdles, yet shows promise and could potentially mitigate the current problems associated with poor patient compliance. Full article
(This article belongs to the Special Issue Ocular Drug Delivery)
227 KiB  
Review
Delivery of Intraocular Triamcinolone Acetonide in the Treatment of Macular Edema
by Aaron Pickrell, Alon Harris, Sandra Ngo, Annahita Amireskandari, Erin Stewart and Brent Siesky
Pharmaceutics 2012, 4(1), 230-242; https://doi.org/10.3390/pharmaceutics4010230 - 15 Mar 2012
Cited by 5 | Viewed by 9868
Abstract
Macular edema (ME) is one of the eventual outcomes of various intraocular and systemic pathologies. The pathogenesis for ME is not yet entirely understood; however, some of the common risk factors for its development have been identified. While this investigation will not discuss [...] Read more.
Macular edema (ME) is one of the eventual outcomes of various intraocular and systemic pathologies. The pathogenesis for ME is not yet entirely understood; however, some of the common risk factors for its development have been identified. While this investigation will not discuss the numerous etiologies of ME in detail, it appraises the two most widely studied delivery modalities of intraocular corticosteroids in the treatment of ME—intravitreal injection (IVI) and sub-Tenon’s infusion (STI). A thorough review of the medical literature was conducted to identify the efficacy and safety of IVI and STI, specifically for the administration of triamcinolone acetonide (TA), in the setting of ME in an attempt to elucidate a preferred steroid delivery modality for treatment of ME. Full article
(This article belongs to the Special Issue Ocular Drug Delivery)
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96 KiB  
Review
Ophthalmic Drug Delivery in Glaucoma—A Review
by Ingrida Januleviciene, Lina Siaudvytyte and Ruta Barsauskaite
Pharmaceutics 2012, 4(1), 243-251; https://doi.org/10.3390/pharmaceutics4010243 - 21 Mar 2012
Cited by 27 | Viewed by 6778
Abstract
Glaucoma is a progressive optic neuropathy and medical therapy is the initial option for the treatment of this potentially blinding condition. Topical instillation of eye drops from the bottle is the most common glaucoma drug delivery form. Due to limited permeability of anterior [...] Read more.
Glaucoma is a progressive optic neuropathy and medical therapy is the initial option for the treatment of this potentially blinding condition. Topical instillation of eye drops from the bottle is the most common glaucoma drug delivery form. Due to limited permeability of anterior ocular surface, natural clearance and drainage, eye drops contain large amounts of inactive ingredients. Effective penetration enhancers are known as irritants causing ocular discomfort. Although drug efficacy is determined by active ingredients, inactive agents can affect tolerance and can result in conjunctival irritation and hyperemia and influence patients’ adherence and quality of life. Full article
(This article belongs to the Special Issue Ocular Drug Delivery)
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