Status of Abandoned Children: A Comparative Study of Islamic and Pakistani Law

This paper deals with the rights of abandoned children in the context of Pakistani society. The main issue is regarding legal status of such children which results in violation of their rights. Islamic law provides for rules for abandoned children which can be provided as a source for legislation in Pakistan. The paper argues that there is a need to formulate a clear legislation to ensure rights and protection of abandoned children. Currently the laws enacted in Pakistan lack provisions related to abandoned children. On the one hand the solutions like adoption/kafalah should be channelized and regularized and on the other hand serious efforts should be made to create awareness regarding rights of abandoned children among the masses. This is a comparative study which discusses and analyses relevant provisions in Islamic as well as Pakistani law.

Formulation Development and In-Vivo Performance of Pharmaceutical Cocrystals

Formulation Development and in-vivo Performance of Pharmaceutical Cocrystals The use of soluble cocrystal for delivering drugs with low solubility, although a potentially effective approach, often suffer from the problem of rapid disproportionation during dissolution, which negates the solubility advantages offered by the cocrystal. This necessitates their robust stabilization in order for successful use in a tablet dosage form. The cocrystal between carbamezepine and succinic acid (CBZ-SUC) exhibits a higher aqueous solubility than its dihydrate, which is the stable form in water. Using this model system, I demonstrate an efficient and material-sparing tablet formulation screening approach enabled by intrinsic dissolution rate measurements. Three tablet formulations capable of stabilizing the cocrystals both under accelerated condition of 40oC and 75% RH and during dissolution were developed using three different polymers, Soluplus® (F1), Kollidon VA/64 (F2) and Hydroxypropyl methyl cellulose Acetate sucinate (F3). When compared to a marketed product, Epitol® 200 mg tablets (F0), drug release after 60 min from formulations F1 (~82%), F2 (~95%) and F3 (~95%) was all higher than that from Epitol® (79%) in a modified simulated intestinal fluid. Studies in albino rabbits showed correspondingly better bioavailability of F1 – F3 than Epitol® tablets. All the three experimental formulations gave statistically significant improvements in AUC0-72 of CBZ than Epitol tablets by applying ANOVA followed by Tukey’s post hoc test (*P˂0.05 for F0-F1, ***P˂0.05 F0-F2, ***P˂0.05 F0-F3). Among the three formulations, F2 tablet formation was the best based on both in-vitro and in-vivo evaluations. Towards the second formulation approach, I first used common polymers to study the supersaturation of carbamezepine-succinic acid (CBZ-SUC) cocrystal at different conditions. In-situ Raman spectroscopy was used to monitor the solid phase during dissolution studies. The solid phase at the end of each experiment was characterized by FTIR and powder X-Ray diffractometry. In-vivo study was performed on selected xi suspension formulations. In absence of polymers, no dissolution advantage was attained by cocrystals due to rapid crystallization of CBZ dihydrate. At room temperature Polyvinyl pyrrolidone (PVP) at concentration of 2% w/v did not stabilize the supersaturated solution, whereas polymer concentration of 0.025% w/v hydroxypropyl methyl cellulose acetate succinate (HPMCAS) stabilized the cocrystal and enhanced the solubility of CBZ in buffer solution at pH 6.8 by 3.2folds to that of stable dihydrate form. A formulation of CBZ-SUC cocrystal containing HPMCAS as a crystallization inhibitor and soluplus® as solubilizer, superior in-vitro dissolution performance was achieved compare to pure CBZ having similar composition at 37±1Ċ. Pharmacokinetic studies in rabbits showed that one of the formulations F7-X (1% w/v cocrystal, 1% w/v HPMCAS and 2% w/v soluplus®), caused around 6folds enhancement in AUC0-72 (***P˂ 0.05), and also led to a much higher Cmax of 4.73 μg/mL than 1.07 μg/mL Cmax of ‘neat’ cocrystal given orally. Also, the F7-X outperformed a reference formulation of CBZ by {1.37folds AUC0-72 of cocrystal formulation (***P˂ 0.05) and Cmax of 3.9 μg/mL} with similar composition to F7-X.