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Title: Dissolution Enhancement of Atorvastatin Calcium as a Model Poorly Soluble Drug
Authors: Reham Hameid Al-Kazemi 
Supervisor: Prof. Aly Nada
Keywords: Drug : Calcium
Issue Date: 2017
Publisher:  Kuwait university - college of graduate studies
Abstract: Atorvastatin calcium (ATC) is an oral anticholesteremic agent, which belongs to BCS class II drug that have high permeability but low aqueous solubility. To get beneficial therapeutic effects, its solubility and dissolution rate need to be improved. In the present study, attempt was made to improve ATC dissolution rate by formulating it into cocrystals using glucosamine and nicotinamide as highly water soluble coformers. Two methods were used for preparing the cocrystals, which included solvent drop grinding (SDG) and solvent evaporation (SE) methods in 1:1, 1:3, and 1:10 drug-coformer molar ratio. The prepared cocrystals showed improved solubility and dissolution rate as compared to the pure drug. The optimized batches were GL2 and NL2, which prepared by SDG method in 1:3 drug-coformer molar ratio, using glucosamine and nicotinamide respectively. The cocrystals formed were characterized by Fourier Transform Infrared (FT-IR), Differential Scanning Calorimetry (DSC), Powder X-ray Diffraction (PXRD), Mass Analysis (MS), Scanning Electron Microscopy (SEM), solubility studies, and dissolution rate studies. DSC and FT-IR spectra of the cocrystals were different from the untreated drug, the coformers, and the physical mixtures indicating their interaction. PXRD patterns of the cocrystals were less intense with new peaks formed compared to untreated ATC. Faster dissolution rate was seen for the cocrystals as compared to both the untreated ATC and the corresponding physical mixtures. The cocrystals GL2 released 98.15 % of the drug within 30 min and drug solubility was enhanced by 31.05 %. NL2 cocrystals completely released all the drug within 30 min and the drug solubility was enhanced by 86.19 %. The cocrystals were formulated into tablet dosage form through direct compression method, which maintained the enhanced dissolution rate of the powder cocrystals. These formulated tablets also showed satisfactory results for various physicochemical evaluation tests. The stability of the powder cocrystals and the formulated tablets were studied at room temperature and at 40 ± 2˚C/75 ± 5% RH and it showed excellent resistance to these storage conditions. In addition, FT-IR, DSC, and PXRD were used to study the effect of storage conditions on the drug-excipients compatibility, which showed that no incompatibility was found in all tablet formulations.
Appears in Programs:1100 Pharmaceutical Sciences

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