قواعد الترجيح المتعلقة بالنص القرآني: دراسة وصفية تطبيقية

After reading the whole books and find out the interpretation, there were various sayings, the meanings and interpretations of the verses of Quran. The reader does not have the capability to select correct and incorrect. He does not know what to do about the various interpretations. At first the people of Mecca knew the status of Revelation; they do not need to explain that revelation, because it was their native language while the Prophet (S.A.W) explains it in detail. After the earlier periods, it was necessary to adapt some rules to know the correct sayings, that rules were already include the Quran itself, in the Sunnah, in the Quranic Sciences, in the books of fundamentals of Jurisprudence, and in the books of Quranic  Sciences. Later on, however, wrote the books as contemporary independent science as such as book of Husain Al Ḥarbī  named (قواعد الترجيح عند المفسرين) and book written by Khalid Al Sabbath named (قواعد التفسير جمعاً ودراسةً). These rules of preference are most important as with the help of these rules, the books of interpretation can be clarified from incorrect sayings. These rules are various, including, related to Quranic text, Sunnah, the views of Companions, the evidence, or related to the linguistics of Arabs. The preference proves the strength of a saying or strengthens an aspect than others through rules of preference. One of the objectives of this research is that the rules of preference can distinguish between correct and incorrect interpretation. The researcher recommended attention to these rules of preference and to study it as a separate subject to get full benefit from the books of interpretation.

Solubility Enhancement of Acyclovir Using Various Techniques and In-Vitro, In-Vivo Evaluation

Solubility of a compound has utmost significance while formulating a compound into a desired dosage form. Solubility is referred to the ability of a substance to get dissolved in a solvent to form a homogenous solution. More than 70% of newly discovered drugs or drugs those are currently under any process present solubility issues. Due to low solubility, major portion of drug is eliminated from body without showing any therapeutic effect. Drugs to be used for therapeutic purposes must have certain solubility. Solubility promotes bioavailability of drugs within the body. Acyclovir (ACV) is a drug of choice against herpes simplex virus (HSV-I & HSV-II), Varicella zoster virus (VZV), Epstein bar virus (EBV), Cytomegalovirus (CMV) and Human herpes virus (HHV-6). It has no distinct BCS classification i.e., at 200 mg it is placed in BCS-III and at 800 mg it is placed in BCS-IV. Daily dose of acyclovir is 200 mg five times a day or 400 mg thrice a day due to its poor bioavailability (15% – 30%). ACV is an ampholyte that shown variable solubilities at acidic and basic pH. A large number of techniques are presented in literature to overcome solubility issues of poorly water soluble drugs like micronization, prodrug formation, addition of surfactants, cyclodextrin complexation, salt formation and crystal modification. Conversion of crystalline to amorphous (more soluble) state occurs in solid dispersions, inclusion complexes, rapid dissolving tablets, hydrogels, hydrogel microparticles, microemulsions, hydrosols, nanosuspensions, inter penetrating networks etc. A wide variety of polymers are currently employed to improve solubility of least soluble active moieties. These include polyvinyl pyrollidone, polyvinyl alcohol, chitosan, superdisintegrants, surfactants, β-cyclodextrin and hydroxypropyl β- cyclodextrin (HP-βCD) etc. Cyclodextrins are natively very active players in enhancing solubility and permeability of BCS class II and class IV drugs thereby, moving them to higher class of BCS classification. In present work, efforts have been made for solubility enhancement of acyclovir through solvent evaporation, kneading technique, direct compression method and free radical polymerization by forming solid dispersions, inclusion complexes, rapid dissolving tablets and hydrogel microparticles. Developed formulations were xxcharacterized by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Thermal gravimetric analysis (TGA), Powder X-Ray Diffractometry (PXRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), solubility studies, entrapment efficiency, product yield, in-vitro dissolution studies and stability studies. Microparticles were characterized by micromeritic properties i.e. angle of repose, bulk density, tapped density, Carr’s compressibility index, and Hausner’s ratio. Fabricated tablets were subjected for weight variation, friability, disintegration time, wetting volume, water absorption ratio. Additionally, ex-vivo permeability studies were conducted on chicken intestine. Kinetic models i.e. zero order, first order, Higuchi and Korsemeyer Peppas were applied on release data to find out best fit model and to confirm mechanism of release followed. Two types of hydrogel microparticles i.e. Beta cyclodextrin grafted methacrylic acid (β-CD-g-MAA) and Beta cyclodextrin grafted 2-acrylamido-2-methylenepropane sulfonic acid (β-CD-g-AMPS). In spite of all characteristic parameters, β-CD-g-MAA hydrogels were evaluated for successful ACV loading through energy dispersive spectroscopy (EDS). Results were also statistically analyzed by one-way analysis of variance (ANOVA) and p value was determined to check significant results. Complex formation and stability of complexed products was confirmed by FTIR and thermal studies, respectively. Transition from crystalline nature to amorphous nature was observed through PXRD studies. Surface morphology and particle dimensions recorded from scanning electron microscopy, it revealed porous surfaces in RDT’s, irregular to uniform size microparticles with smooth surfaces in case of microparticles i.e. solid dispersions and inclusion complexes and highly porous surfaces in case of hydrogel microparticles. Presence of pores promotes rapid uptake of media and dissolution of drug. Internal morphology confirmed successful loading of ACV. Zeta size and potential confirmed micrometric size range of prepared microparticles and neutral or slightly negative charge assured their stability. Wetting time, wetting volume, water absorption ratio and disintegration time for RDT’s were 38 ± 1.10 – 73 ± 1.20 sec, 13 ± 1.25 – 25 ± 1.15 mL, 1.20 ± 0.20 – 1.75 ± 0.02 and 31 ± 2.58 – 67 ± 1.50 sec, respectively for all RDT formulations (F1 – F12). Maximum diffused drug in ex-vivo studies across chicken intestine was 83% (F3). In- xxivitro release studies have shown that major portion almost 98% of ACV was released within 18mins in RDT’s. Microparticles had shown variable ACV release i.e. 12.33% – 85% (SD1 – SD5), 8.76% – 79% (IC1 – IC5) at pH 7.4 and 14.82% – 89% (SD1 – SD5), 12% – 84.9% (IC1 – IC5) at pH 1.2. ACV release from hydrogel microparticles was triggered through pH changes. AMPS based hydrogel microparticles presented pH independent release but more release at basic pH 7.4 when compared to release at pH 1.2. Similarly, MAA based hydrogel microparticles had shown more release at pH 7.4 as compared to pH 1.2. First order release was observed in all formulations i.e. IC’s, SD’s, RDT’s and hydrogel microparticles. Solubility studies of pure ACV and fabricated products were conducted in phosphate buffer of pH 1.2, pH 7.4 and in pure water. Solubility enhancement for microparticles (IC’s and SD’s) that there was significant increase solubility of drug in water (6.18 folds), pH 1.2 (8.78 folds) and pH 7.4 (5.98 folds). In case of RDT’s significant increase in solubility was observed i.e. 10.98 folds, 7.61 folds and 10.13 folds rise in pH 1.2, 7.4 and in water. Solubility of ACV in methacrylic acid containing hydrogel microparticles was promoted in all three solutions i. e. pH 1.2 (2.81 folds), pH 7.4 (9.45 folds) and water (7.39 folds). In case of AMPS based hydrogel microparticles, increase in solubility of ACV i.e. pH 1.2 (10.66 folds), pH 7.4 (8.90 folds) and in water (9.21 folds) was noted. These findings proved that solubility of ACV was promoted in all adapted techniques. Pharmacokinetic data had also depicted that C max and AUC 0-12 were also greater for prepared formulations in contrast to ACV oral powder. Elimination half-life of drug was reduced upto 2.789 hours (hydrogel microparticles) and 2.1414 hours (RDT’s). Toxicological studies i.e. hematological, biochemical and histological had not shown any toxic event. This study concludes that by using potential approaches i.e. solvent evaporation, kneading technique, rapid dissolving tablets and hydrogel microparticles had successfully improved solubility of acyclovir.