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.
اسی ماہ میں عالمِ تاریخ کا سب سے بڑا حادثہ پروفیسر رائزڈوڈ کی موت ہے، پروفیسر مرحوم سنسکرت، تاریخِ ہند قدیم اور عہدِ بودھ کے مستند عالم تھے۔ آپ کی zbogogid خاصی دقتِ نظر سے دیکھی جاتی ہے۔ ۱۸۴۷ء میں پیدا ہوئے تھے۔
Holy Quran is the most sacred scripture bestowed by Allah Almighty upon his bellowed prophet Muhammad (PBUH). Unlike other scriptures, Allah Almighty himself took the responsibility of safety and safe custody of the Holy Quran. That is why, despite passage of more than 1400 years, the Holy Quran remained intact, wordwise as well as meaningwise and will remain intact till the end of the world. Such a unique status of the Holy Quran could not be tolerated by the enemies of Islam and Prophet of Islam. Therefore, they decided to present Holy Quran as a defective document before its readers. For this purpose, they chose to highlight and exploit the short and abbreviated incidents, described by the Holy Quran, under the term of “Muthashalihat”, by adding and narrating false, nonsense and most astonishing stories, just to divert attention of the readers from the basic learning of Holy Quran, towards un-realistic and bogus stories. Accordingly majority of the readers have shown great interest in these stories, which fall under the title of Israiliat Unfortunately, the said stories are included in dozens of Translations Tafaseer of the Holy Quran. In order to acquaint readers of the actual status of Israiliat, the undersigned has started working on the subject. Since Tafseer-e-Jalalain is included in the Syllabus of Maddaris and being taught for the last many years, therefore, I have chosen the same in the first instance, and pray Allah Almighty to help me out in completing my assignment.
This research work was planned to synthesize and characterize transition metal complexes of some biologically active Schiff base chelating agent and then to investigate their antimicrobial and antioxidant activities. The ligands (L1-L5) are the modified forms of pyridine-3-carbaldehyde containing azomethine linkage which is of considerable importance in coordination chemistry. All the ligands were synthesized by reacting pyridine-3-carbaldehyde with primary amines. The structure of the newly synthesized amines were established by IR, NMR, Mass and elemental analysis. The ligands formed complexes of the type [MLX 2 ]. The comparison of the IR spectra of ligands and their metal complexes suggested that pyridine-3-carbaldehyde-N and amine-N are involved in the coordination with the metal ions. The UV-visible spectra of the complexes indicated the tetrahedral geometry for Co(II), Ni(II), Cu(II) and Zn(II) complexes. The antibacterial and antifungal activities of all the compounds were tested against the gram negative bacteria Escherichia coli, Salmonella typhi and Pseudomonas aeruginosa, gram positive bacteria Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumonia and fungal strains Aspergillus Fumigatus, Aspergillus Flavus and Fusarium Solani. Antioxidant activities including Free Radical Scavenging Assay, Nitric Oxide Scavenging Activity, Hydroxyl Radical (OH) Scavenging Activity and Reducing Power were also carried out. Thermal stability of the compounds was studied through TG/DTA.