Special Issue "Solid Dispersions for Drug Delivery: Applications and Preparation Methods"

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 March 2021).

Special Issue Editors

Prof. Dr. Vitaliy Khutoryanskiy
E-Mail Website
Guest Editor
Reading School of Pharmacy, University of Reading, Whiteknights, PO Box 224, Reading RG6 6AD, UK
Interests: pharmaceutical polymers; drug delivery; formulation science; transmucosal drug delivery; biomaterials
Special Issues and Collections in MDPI journals
Dr. Hisham Al-Obaidi
E-Mail Website
Guest Editor
The School of Pharmacy, University of Reading, Reading RG6 6AD, UK
Interests: amorphous polymeric solid dispersions; pulmonary drug delivery; oral drug delivery; co-crystals; co-amorphous dispersions

Special Issue Information

Dear Colleagues,

Manuscripts are invited for publication in a Special Issue of Pharmaceutics entitled "Solid Dispersions for Drug Delivery: Applications and Preparation Methods". This Special Issue is focused on poorly-soluble drugs formulated as solid dispersions. Formation of solid dispersions, where poorly-soluble active pharmaceutical ingredients are dispersed in a solid carrier, is one of the strategies to improve drug dissolution profiles and to enhance bioavailability. These solid drug dispersions could be formulated with the use of water-soluble or insoluble polymers as well as some small molecular weight materials such as surfactants, sugars, and other drugs. Recent advances in this area of research have shown potential application of co-amorphous and polymeric amorphous solid dispersions to enhance solubility and as well as to deliver combination treatments. Likewise, pharmaceutical co-crystals have attracted significant interest to deliver combination treatments. The drug present in amorphous dispersions typically undergoes rapid dissolution, which may result in its better bioavailability. There are several methods used to prepare solid drug dispersions, which include solvent evaporation, melting, and supercritical fluid technology. Numerous solvent evaporation approaches may also involve the use of spray drying, lyophilization, co-precipitation, electrospraying, electrospinning, etc. There are also several melting approaches such as hot-melt extrusion and melt agglomeration.

Prof. Dr. Vitaliy Khutoryanskiy
Dr. Hisham Al-Obaidi
Guest Editors

Manuscript Submission Information

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Keywords

  • solid dispersions
  • poorly-soluble drugs
  • amorphous dispersions
  • crystallinity
  • polymer–drug mixtures
  • solid dosage forms
  • dissolution properties
  • co-crystals

Published Papers (6 papers)

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Research

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Open AccessArticle
Mutual Effects of Hydrogen Bonding and Polymer Hydrophobicity on Ibuprofen Crystal Inhibition in Solid Dispersions with Poly(N-vinyl pyrrolidone) and Poly(2-oxazolines)
Pharmaceutics 2021, 13(5), 659; https://doi.org/10.3390/pharmaceutics13050659 - 04 May 2021
Viewed by 262
Abstract
Poly(N-vinyl pyrrolidone) (PVP), poly(2-methyl-2-oxazoline) (PMOZ), poly(2-ethyl-2-oxazoline) (PEOZ), poly(2-n-propyl-2-oxazoline) (PnPOZ), and poly(2-isopropyl-2-oxazoline) (PiPOZ) were used to prepare solid dispersions with ibuprofen (IB), a model poorly-water soluble drug. Dispersions, prepared by solvent evaporation, were investigated using powder X-ray diffractometry, differential scanning [...] Read more.
Poly(N-vinyl pyrrolidone) (PVP), poly(2-methyl-2-oxazoline) (PMOZ), poly(2-ethyl-2-oxazoline) (PEOZ), poly(2-n-propyl-2-oxazoline) (PnPOZ), and poly(2-isopropyl-2-oxazoline) (PiPOZ) were used to prepare solid dispersions with ibuprofen (IB), a model poorly-water soluble drug. Dispersions, prepared by solvent evaporation, were investigated using powder X-ray diffractometry, differential scanning calorimetry, and FTIR spectroscopy; hydrogen bonds formed between IB and all polymers in solid dispersions. PMOZ, the most hydrophilic polymer, showed the poorest ability to reduce or inhibit the crystallinity of IB. In contrast, the more hydrophobic polymers PVP, PEOZ, PnPOZ, and PiPOZ provided greater but similar abilities to reduce IB crystallinity, despite the differing polymer hydrophobicity and that PiPOZ is semi-crystalline. These results indicate that crystallinity disruption is predominantly due to hydrogen bonding between the drug molecules and the polymer. However, carrier properties affected drug dissolution, where PnPOZ exhibited lower critical solution temperature that inhibited the release of IB, whereas drug release from other systems was consistent with the degree of ibuprofen crystallinity within the dispersions. Full article
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Open AccessArticle
Amorphous Solid Dispersion Tablets Overcome Acalabrutinib pH Effect in Dogs
Pharmaceutics 2021, 13(4), 557; https://doi.org/10.3390/pharmaceutics13040557 - 15 Apr 2021
Viewed by 487
Abstract
Calquence® (crystalline acalabrutinib), a commercially marketed tyrosine kinase inhibitor (TKI), exhibits significantly reduced oral exposure when taken with acid-reducing agents (ARAs) due to the low solubility of the weakly basic drug at elevated gastric pH. These drug–drug interactions (DDIs) negatively impact patient [...] Read more.
Calquence® (crystalline acalabrutinib), a commercially marketed tyrosine kinase inhibitor (TKI), exhibits significantly reduced oral exposure when taken with acid-reducing agents (ARAs) due to the low solubility of the weakly basic drug at elevated gastric pH. These drug–drug interactions (DDIs) negatively impact patient treatment and quality of life due to the strict dosing regimens required. In this study, reduced plasma drug exposure at high gastric pH was overcome using a spray-dried amorphous solid dispersion (ASD) comprising 50% acalabrutinib and 50% hydroxypropyl methylcellulose acetate succinate (HPMCAS, H grade) formulated as an immediate-release (IR) tablet. ASD tablets achieved similar area under the plasma drug concentration–time curve (AUC) at low and high gastric pH and outperformed Calquence capsules 2.4-fold at high gastric pH in beagle dogs. In vitro multicompartment dissolution testing conducted a priori to the in vivo study successfully predicted the improved formulation performance. In addition, ASD tablets were 60% smaller than Calquence capsules and demonstrated good laboratory-scale manufacturability, physical stability, and chemical stability. ASD dosage forms are attractive for improving patient compliance and the efficacy of acalabrutinib and other weakly basic drugs that have pH-dependent absorption. Full article
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Open AccessArticle
Green Nanotechnology in the Formulation of a Novel Solid Dispersed Multilayered Core-Sheath Raloxifene-Loaded Nanofibrous Buccal Film; In Vitro and In Vivo Characterization
Pharmaceutics 2021, 13(4), 474; https://doi.org/10.3390/pharmaceutics13040474 - 01 Apr 2021
Viewed by 266
Abstract
Green nanotechnology utilizes the principles of green chemistry to formulate eco-friendly nanocarrier systems to mitigate patients and environment hazards. Raloxifene (RLX) demonstrates poor aqueous solubility (BCS class II) and low bioavailability, only 2% (extensive first-pass metabolism). The aim of this study is to [...] Read more.
Green nanotechnology utilizes the principles of green chemistry to formulate eco-friendly nanocarrier systems to mitigate patients and environment hazards. Raloxifene (RLX) demonstrates poor aqueous solubility (BCS class II) and low bioavailability, only 2% (extensive first-pass metabolism). The aim of this study is to enhance RLX solubility and bioavailability via development of novel solid dispersed multilayered core-sheath RLX-loaded nanofibers (RLX-NFs) without the involvement of organic solvents. A modified emulsion electrospinning technique was developed. Electrospinning of an RLX-nanoemulsion (RLX-NE) with polymer solution (poly vinyl alcohol (PVA), hydroxypropyl methylcellulose (HPMC), and chitosan (CS) in different volume ratios (1:9, 2:8, and 4:6) using D-optimal response surface methodology was adopted. In vitro characterization of RLX-loaded NFs was performed; scanning electron microscope (SEM), thermal analysis, drug content, release studies, and bioadhesion potential. The optimum NFs formula was evaluated for morphology using high-resolution transmission electron microscopy (HRTEM), and ex vivo drug permeation. The superiority of E2 (comprising RLX-NE and PVA (2:8)) over other NF formulae was statistically observed with respect to Q60 (56.048%), Q240 (94.612%), fiber size (594.678 nm), mucoadhesion time 24 h, flux (5.51 µg/cm2/h), and enhancement ratio (2.12). RLX pharmacokinetics parameters were evaluated in rabbits following buccal application of NF formula E2, relative to RLX oral dispersion. E2 showed significantly higher Cmax (53.18 ± 4.56 ng/mL), and relative bioavailability (≈2.29-fold). Full article
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Open AccessArticle
Improved Dissolution Rate and Intestinal Absorption of Fexofenadine Hydrochloride by the Preparation of Solid Dispersions: In Vitro and In Situ Evaluation
Pharmaceutics 2021, 13(3), 310; https://doi.org/10.3390/pharmaceutics13030310 - 27 Feb 2021
Viewed by 509
Abstract
The objective of this study was to enhance dissolution and permeation of a low soluble, absorbable fexofenadine hydrochloride (FFH) by preparing solid dispersions using polyethylene glycol 20,000 (PEG 20,000) and poloxamer 188 as carriers. The phase solubility measurement for the supplied FFH revealed [...] Read more.
The objective of this study was to enhance dissolution and permeation of a low soluble, absorbable fexofenadine hydrochloride (FFH) by preparing solid dispersions using polyethylene glycol 20,000 (PEG 20,000) and poloxamer 188 as carriers. The phase solubility measurement for the supplied FFH revealed a linear increase in the solubility of fexofenadine with increasing carrier concentration in water (1.45 mg/mL to 11.78 mg/mL with 0% w/v to 30% w/v PEG 20,000; 1.45 mg/mL to 12.27 mg/mL with 0% w/v to 30% w/v poloxamer 188). To select the appropriate drug carrier concentration, a series of solid dispersions were prepared in the drug carrier weight ratios of 1:1, 1:2 and 1:4 by fusion method. The solid dispersions composed of drug carrier at 1:4 weight ratio showed highest dissolution with the time required for the release of 50% of the drug <15 min compared to the supplied FFH (>120 min). The intestinal absorption study presented a significant improvement in the absorption of drug from the solid dispersions composed of poloxamer 188 than PEG 20,000. In summary, the solid dispersions of FFH prepared using PEG 20,000 and poloxamer 188 demonstrated improved dissolution and absorption than supplied FFH and could be used to improve the oral bioavailability of fexofenadine. Full article
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Open AccessArticle
Novel Solid Dispersions of Naphthoquinone Using Different Polymers for Improvement of Antichagasic Activity
Pharmaceutics 2020, 12(12), 1136; https://doi.org/10.3390/pharmaceutics12121136 - 24 Nov 2020
Viewed by 496
Abstract
IVS320 (3a,10b-dihydro-1H-cyclopenta[b]naphtho[2,3-d]furan-5,10-dione) is a naphthoquinone that has low solubility in aqueous medium, a physical behavior that limits its biological activities, considering that compounds from this class have several activities. In this work, solid dispersions (SDs) prepared between [...] Read more.
IVS320 (3a,10b-dihydro-1H-cyclopenta[b]naphtho[2,3-d]furan-5,10-dione) is a naphthoquinone that has low solubility in aqueous medium, a physical behavior that limits its biological activities, considering that compounds from this class have several activities. In this work, solid dispersions (SDs) prepared between IVS320 and polymers hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG), and polyvinylpyrrolidone (PVP) were developed using physical mixture (PM), kneading (KN), and rotary evaporation (RE) methods. Dispersions were investigated using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetry (TG), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). In addition, in vitro antiparasitic activity in Trypanosoma cruzi Y strains was evaluated. Physical-chemical characterization demonstrated the formation of SDs through the interaction of IVS320 with polymeric matrices. SDs of IVS320-polymer presented a significant potentiation of antichagasic activity, with inhibitory growth around 62% (IVS320-HPMC/RE), 55% (IVS320-PEG/RE), and 85% (IVS320-PVP/RE), while pure IVS320 showed a value of 48% for the highest concentrations evaluated (50 µg/mL). Full article
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Review

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Open AccessReview
Therapeutic Applications of Solid Dispersions for Drugs and New Molecules: In Vitro and In Vivo Activities
Pharmaceutics 2020, 12(10), 933; https://doi.org/10.3390/pharmaceutics12100933 - 30 Sep 2020
Cited by 1 | Viewed by 820
Abstract
This review aims to provide an overview of studies that address the use, in therapeutic applications, of solid dispersions (SDs) with biological activities in vitro and/or in vivo mainly made up of polymeric matrices, as well as to evaluate the bioactive activity of [...] Read more.
This review aims to provide an overview of studies that address the use, in therapeutic applications, of solid dispersions (SDs) with biological activities in vitro and/or in vivo mainly made up of polymeric matrices, as well as to evaluate the bioactive activity of their constituents. This bibliographic survey shows that the development of solid dispersions provides benefits in the physicochemical properties of bioactive compounds, which lead to an increase in their biological potential. However, despite the reports found on solid dispersions, there is still a need for biological assay-based studies, mainly in vivo, to assist in the investigation and to devise new applications. Therefore, studies based on such an approach are of great importance to enhance and extend the use of solid dispersions in the most diverse therapeutic applications. Full article
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