Development of prednisone: Polyethylene glycol 6000 fast-release tablets from solid dispersions: Solid-state characterization, dissolution behavior, and formulation parameters

Allopurinol is a commonly used drug in the treatment of chronic gout or hyperuricaemia associated with treatment of diuretic conditions. One of the major problems with the drug is that it is practically insoluble in water, which results in poor bioavailability after oral administration. In the present study, solid dispersions of allopurinol were prepared by solvent evaporation, kneading method, co-precipitation method, co-grinding method and closed melting methods to increase its water solubility. Hydrophilic carriers such as polyvinylpyrrolidone, polyethylene glycol 6000 were used in the ratio of 1:1, 1:2 and 1:4 (drug to carrier ratio). The aqueous solubility of allopurinol was favored by the presence of both polymers. These new formulations were characterized in the liquid state by phase solubility studies and in the solid state by differential scanning calorimetry, powder X-ray diffraction, UV and Fourier Transform Infrared spectroscopy. Solid state characterizations indicated that allopurinol was present as an amorphous material and entrapped in polymer matrix. In contrast to the very slow dissolution rate of pure allopurinol, the dispersion of the drug in the polymers considerably enhanced the dissolution rate. Solid dispersion prepared with polyvinylpyrrolidone showed highest improvement in wettability and dissolution rate of allopurinol. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model and the drug release kinetics primarily as Non-Fickian diffusion. Therefore, the present study showed that polyvinylpyrrolidone and polyethylene glycol 6000 have a significant solubilizing effect on allopurinol.

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Physicochemical characterization and in vitro dissolution behavior of olanzapine-mannitol solid dispersions

Brazilian Journal of Pharmaceutical Sciences ◽

10.1590/s1984-82502012000200008 ◽

2012 ◽

Vol 48 (2) ◽

pp. 243-255 ◽

Cited By ~ 5

Author(s):

Venkateskumar Krishnamoorthy ◽

Suchandrasen ◽

Verma Priya Ranjan Prasad

Keyword(s):

Solid State ◽

Solid Dispersions ◽

In Vitro Dissolution ◽

Dissolution Behavior ◽

Phase Solubility ◽

Permeation Studies ◽

Ft Ir ◽

Solubility Studies ◽

Solid State Characterization

The objective of the present work is to study the dissolution behavior of olanzapine from its solid dispersions with mannitol. Solid dispersions were prepared by melt dispersion method and characterized by phase solubility studies, drug content and in vitro dissolution studies. The best releasing dispersions were selected from release data, dissolution parameters and their release profiles. Solid state characterization techniques like Fourier transform infrared (FT-IR) spectroscopy, X-ray diffractometry, differential scanning calorimetry, near-infrared and Raman spectroscopy were used to characterize the drug in selected dispersions. The dispersions were also evaluated by wettability studies and permeation studies. The results of phase solubility studies and the thermodynamic parameters indicated the spontaneity and solubilization effect of the carrier. The release study results showed greater improvement of drug release from solid dispersions compared to pure drug, and the release was found to increase with an increase in carrier content. The possible mechanism for increased release rate from dispersions may be attributed to solubilization effect of the carrier, change in crystal quality, phase transition from crystalline to amorphous state, prevention of agglomeration or aggregation of drug particles, change in surface hydrophobicity of the drug, and increased wettability and dispersability of the drug in dissolution medium. The suggested reasons for increased release rate from dispersions were found to be well supported by results of solid state characterization, wettability and permeation studies. The absence of any interaction between the drug and the carrier was also proved by FT-IR analysis.

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ChemInform Abstract: Polymeric Amorphous Solid Dispersions: A Review of Amorphization, Crystallization, Stabilization, Solid-State Characterization, and Aqueous Solubilization of Biopharmaceutical Classification System Class II Drugs

ChemInform ◽

10.1002/chin.201642262 ◽

2016 ◽

Vol 47 (42) ◽

Author(s):

Shrawan Baghel ◽

Helen Cathcart ◽

Niall J. O'Reilly

Keyword(s):

Solid State ◽

Classification System ◽

Solid Dispersions ◽

Amorphous Solid ◽

Class Ii ◽

Amorphous Solid Dispersions ◽

Biopharmaceutical Classification System ◽

Solid State Characterization

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Different BCS Class II Drug-Gelucire Solid Dispersions Prepared by Spray Congealing: Evaluation of Solid State Properties and In Vitro Performances

Pharmaceutics ◽

10.3390/pharmaceutics12060548 ◽

2020 ◽

Vol 12 (6) ◽

pp. 548 ◽

Cited By ~ 1

Author(s):

Serena Bertoni ◽

Beatrice Albertini ◽

Nadia Passerini

Keyword(s):

Solid State ◽

Drug Carrier ◽

Solid Dispersions ◽

Class Ii ◽

Water Soluble ◽

Drug Dissolution ◽

Crystalline Solid ◽

Dissolution Behavior ◽

Bcs Class Ii

Delivery of poorly water soluble active pharmaceutical ingredients (APIs) by semi-crystalline solid dispersions prepared by spray congealing in form of microparticles (MPs) is an emerging method to increase their oral bioavailability. In this study, solid dispersions based on hydrophilic Gelucires® (Gelucire® 50/13 and Gelucire® 48/16 in different ratio) of three BCS class II model compounds (carbamazepine, CBZ, tolbutamide, TBM, and cinnarizine, CIN) having different physicochemical properties (logP, pKa, Tm) were produced by spray congealing process. The obtained MPs were investigated in terms of morphology, particles size, drug content, solid state properties, drug-carrier interactions, solubility, and dissolution performances. The solid-state characterization showed that the properties of the incorporated drug had a profound influence on the structure of the obtained solid dispersion: CBZ recrystallized in a different polymorphic form, TBM crystallinity was significantly reduced as a result of specific interactions with the carrier, while smaller crystals were observed in case of CIN. The in vitro tests suggested that the drug solubility was mainly influenced by carrier composition, while the drug dissolution behavior was affected by the API solid state in the MPs after the spray congealing process. Among the tested APIs, TBM-Gelucire dispersions showed the highest enhancement in drug dissolution as a result of the reduced drug crystallinity.

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