عرب عہد جاہلیت میں ’’طلاق‘‘ کا تصور: تحقیقی جائزہ

Conjugal life is an important aspect of human society, on which a prosperous life depends. Almost every Culture, civilization and religion Legislate for family life. There is a part of these laws to end the marital relationship which is denoted by "DIVORCE". Divorce is mentioned in detail in Islamic Sharia, in order to understand them truly one has to genuinely consider and understand the concept of divorce in Pre-Islamic period of ignorance. There were several specific terms for divorce that were used in the Arab culture for example Talᾱq, Īela and Khula etc. But generally decent people use the word "طلاق"(Talᾱq) to end the marital relationship. There were some common causes and reasons for divorce in Arabs before Islam for example lack of mental harmony, infertility, bigotry, family feud and apostasy etc. The divorced women become more and more vulnerable socially and economically in ancient Arab and consequently their children less attention, love and affection of their mothers turning them into rebellious, nonconformist and ruthless individuals crossing all limits of oppression and we often see examples of such incidents in Arabs before dawn of Islam. These cruel customs and practices were uprooted through teachings of Islam which is based on justice, equality and basic human rights.

Design, Fabrication, Formulation and Evaluation of Controlled Realease Matrix Tablets of Clarithromycin

The objective of the present work is to design, formulate and evaluate Clarithromycin controlled release tablets (500 mg) both in-vitro and in-vivo. In this study various Polymers such as Methocel®, Ethocel®, Carbopol, CMC and Eudragit were used for the preparation of the controlled release matrix tablets. Clarithromycin is derivative of erythromycin, belonging to the group of macrolide antibiotics. It is highly effective against Staphylococci, Streptococci, M. catarrhalis, Chlamydia spp., L. pneumophila, B. burgdorferi and Mycoplasma pneumoniae and have moderate activity against H. influenzae and N. gonorrhea. The thorough evaluation of the physical and chemical characteristics was carried out in order to develop the therapeutically effective, stable, safe and reproducible formulation. In the gastrointestinal tract its bioavailability is dissolution rate limited. The pre-formulation studies consist of detailed evaluation of the parameters such as particle size, and particle size distribution. Differential scanning calorimetery (DSC), Fourier transform infrared absorption spectroscopy (FTIR) and X-ray diffractomertery (XRD) were performed as confirmatory techniques. The powder, granules obtained through the wet granulation technique, physical mixture and solid dispersions were thoroughly studied for the tapped density, bulk density, hausner’s ratio angle of repose and car’s compressibility index. Various types of polymers such as Methocel®, Ethocel®, Carbopol, CMC and Eudragit were used were used to control the release rate of the drug and to maintain the desired therapeutic concentration of the drug from the matrix tablets. Different formulation techniques such as wet granulation, solid dispersions and direct compression were used to formulate the controlled release matrix tablets. These tablets were compressed by single punch tableting machine. The prepared matrix tablets were then subjected to the various post formulation physical and chemical tests such as weight variation, dimensional variation, hardness test, friability test, assay and content uniformity tests in order to evaluate the quality of the manufactured tablets. For the test matrix tablets the dissolution study was also carried out in detail. The controlled release matrix tablets formulated by using Methocel® as drug release rate controlling agent in the drug to polymer ratio of 5:2 and formulated by wet granulation technique was shown to be the optimized formulation. Further the pharmacokinetic studies of the optimized formulation of matrix tablets were carried out. For the in-vivo studies albino rabbits were used as experimental animal. For the analysis of blood samples HPLC method was used which was simple, rapid and validated. The test and market brand clarithromycin matrix tablets were given to albino rabbits. The rabbits were fasted for 24 hours. Blood samples were taken from the marginal vein of rabbit at the predetermined time intervals of 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, 42, and 48 hrs after the dose administration. The samples were analyzed by a developed and validated HPLC method. For the investigation of in-vivo drug release mechanism, various types of Chapter – 1: Introduction 26 pharmacokinetic parameters such as t1/2, Cmax, AUC 0-∞, AUCt-∞, AUMC, Kel, Vd, Clt, and Lz were determined by pharmacokinetic software WinNolin® Ver 5.2.1. The preformulation parameters for Clarithromycin pure powder were found to be as bulk density (0.51±0.02), the tapped density (0.64±0.01), hausner’s ratio (1.25), angle repose (30±0.03) and the % compressibility index (20±0.02). The preformulation parameters for the various granules prepared by different formulation techniques were found to be as the bulk density ranged from 0.31±0.02–0.51±0.02, taped density ranged from 0.34±0.05–0.56±0.01, hausner’s ratio range from 1.05±0.04–1.08±0.01, the angle of repose ranged from 12±0.03–55±0.02 and the compressibility index 5±0.03–33.33± 0.02. All the preformulation parameters were found to be in the acceptable range. Post formulation parameters such as hardness, friability, dimensional variations, weight variation, content uniformity, swelling index and muco-adhesive force of the test formulations were studied in detail. The results for these parameters were found to be hardness (7.1±0.07–8.3±0.12), friability (0.1±0.05–0.7±0.08), Thickness (4.4±0.09 –4.7±0.31), weight variation (987±1.25 -1012±0.41) and content uniformity (95%±0.43 – 106±0.43). The swelling index of formulation F 24 (based on Ethocel® as drug release controlling agent in the drug to polymer ratio of 5:3) have minimum swelling tendency (Swelling index; 15.93±2.68) while the formulation F 27 (based on carboxyl methyl cellulose as drug release controlling agent in the drug to polymer ratio of 5:3) have maximum swelling tendency (Swelling index; 80.91±0.31). Muco-adhesive force was shown to be maximum in the formulation F 36 (having Carbopol as drug release controlling polymer used in the drug to polymer ratio of 5:3). Similarly the formulation F 28 (having Eudragit as drug release controlling polymer used in the drug to polymer ratio of 5:1) have shown minimum muco-adhesive force. In-vitro dissolution profile of all the test formulations was evaluated. The formulation F2 was found to be the optimum formulation, which released more than 90% of the drug in 24 hrs. In-vivo pharmacokinetic parameters of the optimum formulation were studied. It was found that the mean elimination rate constants (Kel) of reference Clarithromycin and test were 0.37±0.310/hr and 0.0754±0.016/hr respectively showing the significant difference (P<0.05) in Kel values. Average half-life (t1/2) of Clarithromycin reference and test tablets were found to be 11.48±0.03 to 6.42±0.19, respectively and significant change was detected (P<0.001). The mean Tmax values for reference and test tablets of 2.20±1.32 and 8.33±0.11 hours respectively and Cmax were 17.24±1.08 and 18.66±1.43 μg/mL. Statistical analysis showed significant difference in the values of Tmax reference and test matrix tablets (P<0.05, while there was no significant difference in the values of Cmax of test and reference product clarithromycin (P>0.05). It is concluded that the Methocel® could be used as release rate controlling agent to prepare the matrix tablets of Clarithromycin 500 mg that give the optimum results.