عائلی زندگی اور اُس کے مسائل سے متعلق ابنِ تیمیہ کے فقہی تفردات کا تجزیاتی مطالعہ An analytical study of Ibn Taymiyyah's jurisprudential distinctions Regarding Family Life and its problems

Marriage has been given the status of half-faith, based on which a family is formed, and society is established. Marriage is associated with issues of lineage and inheritance and a section of the Quran describes this subject. The jurists have explained in detail the issues of marriage, dowry, breastfeeding, 'iddah, and alimony under the book of marriage. Ibn Taymiyyah, like other jurisprudential issues, has differed from several jurists on issues related to marriage. For example, it is fair for a man to marry his wife's foster mother and foster daughter. Marriage can take place in any of the terms or words from which the meaning of marriage is derived. Like the father, the grandfather also has the right to marry a minor girl without her permission, it is permissible to marry, the wife has the right to terminate the marriage in case of defect in Haq-e-Mahr, etc. All such jurisprudential dissent will be explained with arguments so that one can be aware of Ibn Taymiyyah's dissent and the arguments behind it. KeyWords: Ibn e Taymiyyah, Jurisprudential Distinctions, Nikaḥ, Kitāb un-Nikaḥ Haq-e-Mahr.

Development and Evaluation of Different Formulations of Meclizine Hydrochloride Pellets

Meclizine HCl is a widely prescribed Antiemetic agent for the therapeutic management of vertigo, formulated and marketed in dosage forms for immediate release. The therapeutically adequate dose, as well as the comparatively shorter half-life (elimination), renders Meclizine HCl as a suitable agent to be prepared as an extended release dosage form. The present study is designed to develop an extended release Meclizine HCl pellet formulations by extrusion spheronization method for which Immediate release pellets and two different type of extended release pellets matrix and coated were prepared Matrix ER pellets were formulated consuming lipids (natural and synthetic). The effect of lipid type, drug/lipid ratio and the different combinations of lipids on drug release, sphericity and shape of pellets were evaluated. Immediate release drug cores were prepared and influence of formulation and process variables were investigated. The effect of type, grade and concentration of coated polymer (acrylic and cellulosic), plasticizer and antitacking agent on drug release, sphericity and shape of pellets were critically assessed. Moreover, a new HPLC method with fluorescence detection was developed and validated for quantification of Meclizine HCl in human plasma in order to compare ER optimized pellet formulation with IR pellet formulation and to further determine the food effect on ER pellet formulation. Four different lipids were used to prepare matrix ER pellet formulations. The lipids used were Glyceryl palmitostearate (Precirol®), Glyceryl monostearate (Geleol®), Carnauba wax and Glyceryl behenate (Compritol®). They were employed either alone or in combinations of drug/lipid ratio ranging from 1:0.5–1:3. Immediate release drug cores were designed using lactose (20-30%), microcrystalline cellulose (45-70%) and polyvinylpyrrolidone (2- 5%) with an optimized amount of granulating water (20-50%). Ethyl cellulose (EC) and Eudragit® coats were applied at variable grades (EC-7P® and 10P®, Eudragit®RL100 and RS100) and amounts (5-10%) using Central Composite Rotatable Design (CCRD). The influence of three coating variables polymer (Eudragit® and EC), plasticizer (TEC and Triacetin) and antitacking agent (Talc) was determined. The responses drug release, time for 90% drug release (T90), aspect ratio and two-dimensional shape factor (eR) were determined for each formulation of the experimental design and their values were used for modeling and process optimization. FTIR (Fourier transform infrared spectroscopy) was conducted to test drug-lipid and drugpolymer interaction which was found to be absent. Flow properties, particle size, moisture content, friability, drug content and drug release of immediate, matrix and coated formulations were determined. The shape of the pellets was characterized by image analysis software. Dissolution studies at variable pH and release kinetics were analyzed. Energy dispersive spectroscopy assessment indicated the elemental composition of all the type of pellets. SEM (Scanning electron microscopy) was performed to reveal the surface morphology of pellet formulations. Accelerated stability was conducted for optimized pellet formulations as per ICH guidelines. A new HPLC method with fluorescence detection was developed and validated for the determination of Meclizine HCl in human plasma. The most optimized formulation was selected for extensive pharmacokinetic profile investigations. It was a single-center, single dose, open-label, randomized, 2-treatment, 2-sequence, 2-period, cross-over comprised of two parts with a separate group of volunteers for each part. Bioequivalence was assessed for Meclizine HCl ER pellets to Meclizine HCl IR pellets in fasted subjects (study 1) and for Meclizine HCl ER pellets in fed and fasted conditions (study 2). The analysis was performed on log-transformed data as per FDA guidelines. Geometric mean ratios (GMRs) and corresponding 90% CIs were determined and Bioequivalence was claimed if the resulting 90% CIs were within the prespecified boundaries (0.800-1.250 or 80%-125%). During formulation and drug design phase, Shape factor (eR) indicative of sphericity varied with the type and the concentration of the lipids. Pellets, highly spherical in shape were successfully obtained with Geleol® (Aspect ratio = 1.005–1.052). The drug release was controlled effectively by employing three (3) lipids in different combinations: (i) Geleol® and Compritol®, (ii) Geleol® and Carnauba wax and (iii) Geleol®, Compritol® and Carnauba wax. Geleol® and Compritol® pellets, scanned with electron microscopy, revealing the smooth surfaces with pores. Irregular rough surface marked with hollow depressions was noted in pellets formulated with Geleol® and Carnauba wax. Kinetics of (i) Geleol® and Compritol® pellets, explained by Korsmeyer-Peppas (R2 = 0.978–0.993) indicated nonFickian diffusion (n = 0.519-0.597). Combinations of (ii) Geleol® and Carnauba wax and (iii) Geleol®, Compritol® and Carnauba wax pellets followed Zero-order (R2 = 0.991– 0.995). Optimized formulations showed the accelerated stability of 37 months. Spherical and firm immediate release drug cores (Aspect ratio=1.010-1.040; eR = 0.980- 0.991) with maximum yield (92%) at rapid extrusion rate were only prepared when MCC was co-processed with PVP followed with spheronization initially at low-speed (800rpm) then at high-speed (1500rpm). The aspect ratio and shape factor of Eudragit® RL100 coated pellets ranged from 1.018-1.085 and 0.714-0.975 respectively. EC 7P® coated pellets were rough with granular (uneven) surface having an aspect ratio (1.014-1.061) and twodimensional shape factor (0.829-0.898). Immediate release core pellets released 80% Meclizine HCl within 45min (USP criteria), therefore, selected for extended release coating. Desired drug release profiles were obtained from Eudragit® RL100 (6% polymer, TEC and talc) and EC10P® (10%) coated pellets. Among all these three factors coated polymer, plasticizer and antitacking agent, the most influencing factor on sphericity, Meclizine HCl release and T90 was the choice of polymer. However, the shape factor eR of coated pellet formulations was also influenced by Plasticizer (TEC, Triacetin) concentration. Pronounced pH effect on drug release profiles was observed for IR drug cores and ER coated pellets irrespective of the type of polymer. SEM showed spherical and intact IR drug cores (L×W=1.34mm) with numerous minute pores on the smooth surface. The number of pores present on the surface of IR cores was reduced after application of thin smooth films of Eudragit® RL100 and EC10P® exhibiting almost similar measurement across different areas of pellet surface. Eudragit® RL100 coated pellets had length × width= 1.54mm×1.59mm. The length and the width of the EC10P® coated pellet were 1.47mm×1.46mm. Kinetics of Meclizine HCl pellets coated with 6% Eudragit® RL100 (FC12-FC15) were best explained by Korsmeyer-Peppas model (R2 = 0.9892-0.9941) followed with Zero-order (R2 = 0.9787-0.9879) and Higuchi model (R2 = 0.9770-0.9882). The kinetics of 10% EC10P® coated pellets were best explained by Korsmeyer-Peppas (R2 = 0.9861-0.9901) and Higuchi’s (R2 = 0.9810-0.9836) models. The similarity test was performed using Eudragit® RL100 coated pellet formulation (FC12) as a reference. Optimized formulations showed the accelerated stability of 45months. The chromatographic separation of Meclizine HCl was achieved by HPLC with a fluorescence detector. The excitation-emission wavelengths of 265-291nm were used for Meclizine HCl and 285-460nm for Ofloxacin (IS). The retention time of Meclizine HCl was 6.2 ± 0.2 min and Ofloxacin was 2.5±0.2min. The linearity of drug samples in the mobile phase and plasma over a concentration range of 10-200ng/ml was achieved with a mean coefficient of correlation R2 = 0.9999. The validation parameters were found within the specified limits. FC12 (Eudragit® RL100 6%, TEC 0.75% and talc 3.75%), the most optimized formulation was selected for the pharmacokinetic study. The mean Cmax of Meclizine HCl IR encapsulated pellets (60mg) was 98.051ng/ml and ER encapsulated pellets was 84.052ng/ml under the fasted state with the GMR (Geometric mean ratio) 0.8572 and associated 90% CI 0.8571-0.8573. The Tmax of the IR encapsulated pellets was 3.029h and ER encapsulated pellets was 5.116h with the GMR 1.6888 having 90% CI (1.6884-1.6893). The mean AUC0- t, and mean AUC0-∞ were 1169.964h⁺ng/ml and 1253.417h⁺ng/ml for IR pellets and 1181.226h⁺ng/ml and 1265.117h⁺ng/ml for ER pellets under fasted condition. The GMR of AUC0-t was 1.0096 with 90% CI (1.0093-1.0100) and 1.0093 for AUC0-∞ with 1.0090- 1.0096 CI at 90%. The mean T1/2Ka (absorption half-life) and mean T1/2Kel (elimination halflife) of IR Meclizine HCl pellets were recorded as 1.795h and 5.448h. The half-lives of ER Meclizine HCl pellets were observed to be 2.872h T1/2Ka and 5.803h T1/2Kel. The GMR of 1.5994 absorption half-life, T1/2Ka (1.5985-1.6002) and 1.0043 elimination half-life, T1/2Kel (1.0033-1.0053) of IR Meclizine HCl reference pellets and ER test pellets were noted with 90%CI under the fasted state. Thus the two formulations were assumed bioequivalent on the basis of primary pharmacokinetic parameters. In part 2 study food did not influence significantly the primary pharmacokinetic parameters of ER Meclizine HCl pellets yielding 84.033ng/ml (fasted) and 80.049ng/ml (fed) Cmax with GMR 0.9526 (0.9524-0.9528), 1181.228h⁺ng/ml (fasted) and 1193.615h⁺ng/ml (fed) AUC0-t with GMR 1.0105 (1.0102-1.0108), 1265.383h⁺ng/ml (fasted) and 1275.111h⁺ng/ml (fed) AUC0-∞ with GMR 1.0077 (1.0073-1.0081). The mean Tmax of the ER encapsulated pellets under both fasted and fed conditions was 5.117h with GMR 1.0903 (1.0900-1.0907). The half-lives of ER Meclizine HCl pellets under fed state were observed to be 2.557h T1/2Ka and 5.646h T1/2Kel.The GMR of 0.8890 absorption half-life, T1/2Ka (0.8739-0.9043) and 0.9718 elimination half-life, T1/2Kel (0.9701-0.9735) of ER Meclizine HCl reference pellets under fasted (reference) and fed (test) state were noted. The matrices for the extended release formulation of the antiemetic agent Meclizine HCl from the extruded-spheronized pellets were formed by using three lipids successfully in different combinations e.g. Geleol®, Compritol® and Carnauba wax. Both Eudragit® RL100 and EC10P® present potential application as film former for extended release of Meclizine HCl from extruded-spheronized IR pellets. The Encapsulated pellets of this antiemetic agent can be used effectively for management of nausea, motion sickness and vertigo for an extended period of time." xml:lang="en_US