Istisnā’- a Realistic Approach to the Concept in Islamic Finance and its Application to the Agricultural Sector in Pakistan

Farmers predominantly belong to lower class of the society, particularly in developing and under developing countries. This actuality really put them on back-foot in every sphere of life, including their various agricultural activities.  For instance, they always face problems to fulfil their agricultural requirement, both for crop and non crop activities, and hence, not in position to get utmost benefits from their efforts. Being citizens of a developing country, Pakistani farmers come across the identical situation. As they are Muslims, therefore, avoid securing interest based loan from the financial institutions. Islamic financial system provides an alternate to such interest based arrangement in the shape of various financing techniques. Among these, Istisnā’ (manufacturing) is the most important one which can be used effectively for the fulfilment of various agricultural requirements. However, its role is more dominant in the satisfaction of non crop agricultural activities that is for example, manufacturing of some heavy agricultural machinery and equipments, installation of tube-wells and channels for appropriate irrigation system, construction of small houses for farmers in their lands etc. The present work discusses the theoretical background of this mode, available in the scholarly work of classical and contemporary Muslim jurists’ work, followed by the description that how it can be used for financing various sectors of agriculture. Study reveals the transaction is equally viable for the development of all sectors of agriculture like local farming, fish farming, dairy farming, poultry farming, horticulture etc. The intended results can be achieved when the financial institutions apply the transaction in its true spirit and philosophies envisaged for it by Islamic commercial law, and not mere a source of earning profit.

Development, Characterization and In-Vivo Evaluation of Pharmaceutical Cocrystals

Background: Oral drug delivery is a great challenge for poorly water soluble drugs. In the past various techniques have been adopted to improve the solubility of lipophilic drugs. Major problem associated with oral drug delivery system is poor bioavailability that is attributed to low solubility and permeability. A pharmaceutical cocrystal is one of the recent techniques for the modification of various pharmaceutical parameters of drugs such as solubility, stability, dissolution and bioavailability. Various cocrystal formers i.e., citric acid, benzoic acid, glutaric acid, glycolic acid, tartaric acid and nicotinamide etc. have been utilized for this purpose. Glipizide belongs to second generation sulphonylureas have low solubility and high permeability. Efforts have been made for solubility enhancement of glipizide through various techniques. However, cocrystalization is another emerging technique for solubility enhancement of BCS-II class drug glipizide. Objective of study: The aim of present work was to develop pharmaceutical cocrystals for solubility enhancement of glipizide using citric acid, nicotinamide, glutaric acid and glycolic acid as a coformer. Statement of novelty: Pharmaceutical cocrystalization technique has adopted in this work for solubility enhancement of poorly water soluble drug, glipizide. So, novelty lies in the synthesis of glipizide cocrystals using different coformers and techniques for improvement of solubility, dissolution as well as in-vivo performance of drug. Methodology: Cocrystals were prepared by four reported methods i.e., solid state grinding, liquid assisted grinding, slurry and solvent evaporation. The effect of formulation parameters such as coformer type, ratio of coformer used as well as type of method employed was studied on solubility and drug release. On the basis of invitro drug release and solubility studies, optimum formulations were selected for further characterization. Micromeritic studies were performed to determine the flow properties of synthesized cocrystals. Particle size was confirmed by optical microscopy and zeta sizer analysis. Fourier Transform Infrared Spectroscopy (FTIR), Powder X-ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), Thermo-gravimetric analysis (TGA) and Scanning Electron Microscopy (SEM) were performed for structural analysis, crystallinity, thermal stability and surface Page XXII morphology determination, respectively. In-vivo studies of optimum formulations i.e., glipizide-citric acid (GPZ-CA) and glipizide-nicotinamide (GPZ-NICO) cocrystals were conducted to determine the pharmacokinetic profile of glipizide. Statistical analysis was also performed through univariate analysis of variance (UANOVA) at 5% level of significance (p-value) to determine the significance of results. Results: GPZ-CA, GPZ-NICO, GPZ-GLU and GPZ-GLY cocrystals were synthesized successfully. Solubility of glipizide was significantly enhanced by cocrystals in water as well as in buffers of pH 1.2 and pH 6.8. Solubility of GPZ-CA cocrystals in distilled water was found 54.75 folds and 55.75 folds from F1 and F8 formulations, respectively. Optimum formulations of GPZ-NICO cocrystals showed 69.5 folds (F2) and 73 folds (F6) increase in water solubility. GPZ-GLU cocrystals showed 53 folds and 54.27 folds improved solubility in distilled water from optimum formulations F3 and F7, respectively. However, solubility enhancement in case of GPZ-GLY cocrystals was found as 52 folds (F4) and 53 folds (F8) from optimum formulations as compared to pure drug. All formulated cocrystals were having good flow properties as confirmed by micromeritic analysis. Optical microscopy and zeta sizer confirmed the particle size of cocrystals in micrometric to nanometric range. SEM revealed variable surface morphology of cocrystals. Presence of glipizide in the form of white steaks on cocrytals was confirmed by SEM. FTIR analysis confirmed the formation of cocrystals. Thermal stability was confirmed by thermal analysis of formulations. Crystalline nature of formulated cocrystals was confirmed by PXRD. Release of glipizide from prepared cocrystals was found to be higher when compared to conventional glipizide. However, maximum drug release was observed at pH 6.8 than pH 1.2 from all formulations. In-vivo studies presented higherCmax and improved pharmacokinetic parameters i.e., AUC(0-24), AUMC(0-24) and shortened Tmax as compared to glipizide in the form of powder. Conclusion: Hence, it was concluded that cocrystals could pave the way for development of an improved design strategy to overcome the solubility and dissolution problems associated with BCS-II class drugs.