Dissolution is an important preceding step for the absorption of drugs in class II of the Biopharmaceutics Classification System (BCS) resulting in poor bioavailability. This current study was directed at determining the outcome of in situ micronization technique on the dissolution and solubility profiles of paracetamol. Six formulations of paracetamol microcrystals were produced by the solvent change method using HPMC and PVP K30 as stabilizing agents. The solubility, percentage drug content, and dissolution patterns of the produced microcrystals were all tested. The study disclosed that paracetamol solubility was increased up to 5-fold in the PVP K30 stabilized paracetamol microcrystal and a 4.5-fold increase for HPMC stabilized paracetamol microcrystal. The time course of dissolution was improved significantly from 0.6%/min for plain paracetamol to 1.1%/min and 1.2%/min for HPMC and PVP K30 stabilized paracetamol microcrystal respectively. Formulation P6, with 0.08 g of PVP K30 as stabilizing agents and an anti-solvent to solvent ratio of 1:6 was the optimized formulation having a 5-fold solubility increase, 98.3% content of active and 95.32% drug release in 60 minutes. The solvent change strategy of the in situ micronization technique could be used for the augmentation of solubility and dissolution of paracetamol.
In a broader mathematical or computational perspective, an optimization problem is defined as a problem of finding the best solution from all feasible solutions. In terms of Machine Learning and…
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F. Huszár, und D. Duvenaud. (2012)cite arxiv:1204.1664Comment: Accepted as an oral presentation at Uncertainty in Artificial Intelligence 2012. Updated to fix several typos.
C. Elliott. (2018)cite arxiv:1804.00746Comment: 37 pages with proof appendices and 15 figures. Extended version of a paper appearing at ICFP 2018. More info at http://conal.net/papers/essence-of-ad/.