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Pharmaceutics
Special Issues
Solubilization and Dissolution Enhancement of Poorly Soluble Drugs
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Solubilization and Dissolution Enhancement of Poorly Soluble Drugs

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Physical Pharmacy and Formulation".

Deadline for manuscript submissions: closed (31 May 2020) | Viewed by 24092

Special Issue Editor

Prof. Dr. Jaehwi Lee

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Guest Editor
College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea
Interests: solubilization; bioavailability; particle technologies; lipid-based drug delivery; formulation design
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

New molecules and even existing drugs suffer considerably from low solubility in aqueous media and thereby demonstrate low oral bioavailability. As the passage through the gastrointestinal tract offers only a short duration of time, the rate at which the solid-state drug goes into aqueous solution is extremely critical for good bioavailability. For improving oral bioavailability, numerous pharmaceutical techniques have been developed to enhance dissolution rates and aqueous solubility of the drug. Particle size reduction is frequently employed to increase the dissolution rate of the drug in solid dosage forms, but is generally unable to increase the aqueous solubility. By contrast, solid dispersion systems of a drug can increase the aqueous solubility of a drug as well as its dissolution rates. There have been new attempts to employ lipids as carriers for the development of solid solutions and dispersions. Thus, I consider it is the right time to launch this Special Issue of Pharmaceutics to specifically introduce and highlight current technologies that can overcome the disadvantages of traditional solubilization techniques as well as newly developed approaches to modify the solubility and dissolution behaviors of a drug. Original papers and review articles concerning solubilization and dissolution enhancement of poorly soluble drugs are all welcome.

Prof. Dr. Jaehwi Lee
Guest Editor

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Keywords

  • poorly soluble drugs
  • solubilization
  • dissolution enhancement
  • amorphization
  • pharmaceutical materials
  • solubilizing excipients

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Published Papers (5 papers)

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Research

17 pages, 7735 KiB  
Article
Impact of HPMCAS on the Dissolution Performance of Polyvinyl Alcohol Celecoxib Amorphous Solid Dispersions
by Marius Monschke and Karl G. Wagner
Pharmaceutics 2020, 12(6), 541; https://doi.org/10.3390/pharmaceutics12060541 - 11 Jun 2020
Cited by 44 | Viewed by 5575
Abstract
Amorphous solid dispersions (ASDs) have been proven to increase the bioavailability of poorly soluble drugs. It is desirable that the ASD provide a rapid dissolution rate and a sufficient stabilization of the generated supersaturation. In many cases, one polymer alone is not able [...] Read more.
Amorphous solid dispersions (ASDs) have been proven to increase the bioavailability of poorly soluble drugs. It is desirable that the ASD provide a rapid dissolution rate and a sufficient stabilization of the generated supersaturation. In many cases, one polymer alone is not able to provide both features, which raises a need for reasonable polymer combinations. In this study we aimed to generate a rapidly dissolving ASD using the hydrophilic polymer polyvinyl alcohol (PVA) combined with a suitable precipitation inhibitor. Initially, PVA and hydroxypropylmethylcellulose acetate succinate (HPMCAS) were screened for their precipitation inhibitory potential for celecoxib in solution. The generated supersaturation in presence of PVA or HPMCAS was further characterized using dynamic light scattering. Binary ASDs of either PVA or HPMCAS (at 10% and 20% drug load) were prepared by hot-melt extrusion and solid-state analytics were conducted using differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and fourier-transformed infrared spectroscopy (FT-IR). The non-sink dissolution studies of the binary ASDs revealed a high dissolution rate for the PVA ASDs with subsequent precipitation and for the HPMCAS ASDs a suppressed dissolution. In order to utilize the unexploited potential of the binary ASDs, the PVA ASDs were combined with HPMCAS either predissolved or added as powder and also formulated as ternary ASD. We successfully generated a solid formulation consisting of the powdered PVA ASD and HPMCAS powder, which was superior in monophasic non-sink dissolution and biorelevant biphasic dissolution studies compared to the binary and ternary ASDs. Full article
(This article belongs to the Special Issue Solubilization and Dissolution Enhancement of Poorly Soluble Drugs)
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20 pages, 3537 KiB  
Article
Design and Characterization of Phosphatidylcholine-Based Solid Dispersions of Aprepitant for Enhanced Solubility and Dissolution
by Sooho Yeo, Jieun An, Changhee Park, Dohyun Kim and Jaehwi Lee
Pharmaceutics 2020, 12(5), 407; https://doi.org/10.3390/pharmaceutics12050407 - 29 Apr 2020
Cited by 29 | Viewed by 4612
Abstract
This study aimed to improve the solubility and dissolution of aprepitant, a drug with poor aqueous solubility, using a phosphatidylcholine (PC)-based solid dispersion system. When fabricating the PC-based solid dispersion, we employed mesoporous microparticles, as an adsorbent, and disintegrants to improve the sticky [...] Read more.
This study aimed to improve the solubility and dissolution of aprepitant, a drug with poor aqueous solubility, using a phosphatidylcholine (PC)-based solid dispersion system. When fabricating the PC-based solid dispersion, we employed mesoporous microparticles, as an adsorbent, and disintegrants to improve the sticky nature of PC and dissolution of aprepitant, respectively. The solid dispersions were prepared by a solvent evaporation technique and characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry, and X-ray powder diffraction. The FTIR results showed that aprepitant interacted with the PC carrier by both hydrogen bonds and van der Waals forces that can also be observed in the interaction between aprepitant and polymer carriers. The solid dispersions fabricated with only PC were not sufficient to convert the crystallinity of aprepitant to an amorphous state, whereas the formulations that included adsorbent and disintegrant successfully changed that of aprepitant to an amorphous state. Both the solubility and dissolution of aprepitant were considerably enhanced in the PC-based solid dispersions containing adsorbent and disintegrant compared with those of pure aprepitant and polymer-based solid dispersions. Therefore, these results suggest that our PC-based solid dispersion system is a promising alternative to conventional formulations for poorly water-soluble drugs, such as aprepitant. Full article
(This article belongs to the Special Issue Solubilization and Dissolution Enhancement of Poorly Soluble Drugs)
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24 pages, 6449 KiB  
Article
The Effect of Cooling on the Degree of Crystallinity, Solid-State Properties, and Dissolution Rate of Multi-Component Hot-Melt Extruded Solid Dispersions
by Dean Hurley, Mark Davis, Gavin M. Walker, John G. Lyons and Clement L. Higginbotham
Pharmaceutics 2020, 12(3), 212; https://doi.org/10.3390/pharmaceutics12030212 - 1 Mar 2020
Cited by 17 | Viewed by 3638
Abstract
The effect of cooling on the degree of crystallinity, solid-state and dissolution properties of multi-component hot-melt extruded solid dispersions [SD] is of great interest for the successful formulation of amorphous SDs and is an area that is unreported, especially in the context of [...] Read more.
The effect of cooling on the degree of crystallinity, solid-state and dissolution properties of multi-component hot-melt extruded solid dispersions [SD] is of great interest for the successful formulation of amorphous SDs and is an area that is unreported, especially in the context of improving the stability of these specific systems. The thermal solid-state properties, degree of crystallinity, drug–polymer interactions, solubility and physical stability over time were investigated. X-ray powder diffraction [XRPD] and hyper differential scanning calorimetry [DSC] confirmed that indomethacin [INM] was converted to the amorphous state; however, the addition of poloxamer 407 [P407] had a significant effect on the degree of crystallinity and the solubility of the SD formulations. Spectroscopy studies identified the mechanism of interaction and solubility studies, showing a higher dissolution rate compared to amorphous and pure INM in pH 1.2 with a kinetic solubility of 20.63 µg/mL and 34.7 µg/mL after 3 and 24 h. XRPD confirmed that INM remained amorphous after 5 months stability testing in solid solutions with Poly(vinylpyrrolidone-co-vinyl acetate) [PVP VA64] and Plasdone S-630 [PL-S630]. Although cooling had a significant effect on the degree of crystallinity and on solubility of INM, the cooling method used did not have any significant effect on the amorphous stability of INM over time. Full article
(This article belongs to the Special Issue Solubilization and Dissolution Enhancement of Poorly Soluble Drugs)
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24 pages, 7290 KiB  
Article
Mechanism and Improved Dissolution of Glycyrrhetinic Acid Solid Dispersion by Alkalizers
by Luning Dong, Yaping Mai, Qiang Liu, Wannian Zhang and Jianhong Yang
Pharmaceutics 2020, 12(1), 82; https://doi.org/10.3390/pharmaceutics12010082 - 20 Jan 2020
Cited by 50 | Viewed by 5202
Abstract
The purpose of this study was to increase the dissolution of glycyrrhetinic acid (GA) by preparing ternary solid dispersion (TSD) systems containing alkalizers, and to explore the modulating mechanism of alkalizers in solid dispersion systems. GA TSDs were prepared by hot melt extrusion [...] Read more.
The purpose of this study was to increase the dissolution of glycyrrhetinic acid (GA) by preparing ternary solid dispersion (TSD) systems containing alkalizers, and to explore the modulating mechanism of alkalizers in solid dispersion systems. GA TSDs were prepared by hot melt extrusion (HME) with Kollidon® VA64 as the carrier and L-arginine/meglumine as the alkalizers. The in vitro release of the TSD was investigated with a dissolution test, and the dissociation constant (pKa) was used to describe the ionization degree of the drug in different pH buffers. Scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Fourier Transform Infrared Spectroscopy (FTIR), Raman spectra, X-ray photoelectron spectroscopy (XPS), and a molecular model were used for solid-state characterizations and to study the dissolution mechanism of the TSDs. It was evident that the dissolution of GA significantly increased as a result of the TSD compared to the pure drug and binary solid dispersion. SEM, DSC, and XPRD data showed that GA transformed into an amorphous form in TSD. As illustrated by FTIR, Raman, XPS, and molecular docking, high binding energy ion-pair complexes formed between GA and the alkalizers during the process of HME. These can destroy the H-bond between GA molecules. Further, intermolecular H-bonds formed between the alkalizers and Kollidon® VA64, which can increase the wettability of the drug. Our results will significantly improve the solubility and dissolution of GA. In addition, the lower pKa value of TSD indicates that higher ionization is beneficial to the dissolution of the drug. This study should facilitate further developments of TSDs containing alkalizers to improve the dissolution of weakly acidic drugs and gain a richer understanding of the mechanism of dissolution. Full article
(This article belongs to the Special Issue Solubilization and Dissolution Enhancement of Poorly Soluble Drugs)
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10 pages, 2537 KiB  
Article
Directly Compressed Tablets of Free Acid Ibuprofen with Nanocellulose Featuring Enhanced Dissolution: A Side-by-Side Comparison with Commercial Oral Dosage Forms
by Athanasios Mantas, Marie-Amélie Petit and Albert Mihranyan
Pharmaceutics 2020, 12(1), 71; https://doi.org/10.3390/pharmaceutics12010071 - 17 Jan 2020
Cited by 6 | Viewed by 4013
Abstract
We have previously reported that heated powder mixtures of ibuprofen (IBU) and high surface area nanocellulose exhibit an enhanced dissolution and solubility of the drug due to IBU amorphization. The goal of the present work was to further elaborate the concept and conduct [...] Read more.
We have previously reported that heated powder mixtures of ibuprofen (IBU) and high surface area nanocellulose exhibit an enhanced dissolution and solubility of the drug due to IBU amorphization. The goal of the present work was to further elaborate the concept and conduct side-by-side in vitro drug release comparisons with commercial formulations, including film-coated tablets, soft gel liquid capsules, and IBU-lysine conjugate tablets, in biorelevant media. Directly compressed tablets were produced from heated mixtures of 20% w/w IBU and high surface area Cladophora cellulose (CLAD), with 5% w/w sodium croscarmelose (AcDiSol) as superdisintegrant. The side-by side studies in simulated gastric fluid, fasted-state simulated intestinal fluid, and fed-state simulated intestinal fluid corroborate that the IBU-CLAD tablets show more rapid and less variable release in various media compared to three commercial IBU formulations. On the sidelines of the main work, a possibility of the presence of a new meta-crystalline form of IBU in mixture with nanocellulose is discussed. Full article
(This article belongs to the Special Issue Solubilization and Dissolution Enhancement of Poorly Soluble Drugs)
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