الدر المختار کا سندھ میں مطالعہ: ایک تحقیقی جائزہ

A well Known book Durr al-Mukhtār has great importance in Ḥanafī School of thought. This is mainly due to its conciseness and comprehensiveness. This is why most of Ḥanafī Scholars has worked on it by editing the manuscripts and writing scholarly footnotes annotation which numbered more than sixty.   Al-Durr al-Mukhtār has remained law book in sub-continent. Sindhi scholars have also written commentaries and footnotes on this master piece of the latter Ḥanafī school of thought. This paper attempts to introduce these standard works in detail. 

Formulation Development of Controlled Release Lornoxicam Capsules by Microencapsulation Technique and its Invitro and in Vivo Characterization

The purpose of the research was: (a) to prepare controlled release microcapsules by spray drying technique, (b) to characterize the properties of these microcapsules, (c) to perform in-vivo bioequivalence studies of developed microcapsules with marketed formulation, (d) to formulate and evaluate microparticles by modified emulsion solvent evaporation (MESE) technique and finally (e) to develop in-vitro in-vivo correlation for the microparticulate batches with differing release rate characteristics of a potent analgesic drug, Lornoxicam. The study successfully achieved microencapsulation of Lornoxicam by spray drying using blend of Eudragit L100 and HPMC 15cps. Spray drying technique is getting more and more attention in pharmaceutical industry due to its numerous advantages. The microparticles obtained were studied for particle size, morphology, drug loading, incorporation efficiency and in-vitro release. The process involved the mixing of ethanol and acetone with polymers to achieve uniform dispersion. The dissolution of microparticles was undertaken in pH 1.2 (first 2 h) and pH 6.8 (for 22 h). FTIR and DSC studies did not reveal considerable incompatibilities in the spectra of drug loaded microparticles as compared to pure drug. The microparticles were ellipsoidal in shape with surface morphology clearly showing presence of drug particles. The incorporation efficiency increased from 56.48% ± 2.21 to 83.04% ± 1.22 with the increase in the polymer contents. Percent loading was in the range of 20.75% ± 0.2 to 32.75% ± 0.2 and was independent of contents of polymer blend. Significant (p<0.05) decrease in release rate of drug was observed by increasing polymer contents from prepared microcapsule batches without affecting extent of release. Typical sustained release pattern occurred at drug: copolymer ratio of 1:3. Results of kinetic models showed pattern of release data to be best fitted to Peppas and first order using DD solver. The „n‟ value ranged from 0.201 to 0.718, indicating drug release both by diffusion and anomalous mechanisms. To perform in-vivo bioequivalence studies, development of a precise and accurate reverse phase HPLC method was carried out for quantitation of Lornoxicam in human plasma. Subsequently, validation parameters were studied for confirming its reproducibility. Separation of analytes was achieved on Eclipse C-18 column (150×4.6mm, 5µm). The mobile phase consisted of combination of phosphate buffer (pH 4.5) and acetonitrile in the ratio of 45:55 v/v and UV detection was set at 376 nm. The linearity, selectivity, accuracy, precision and stability studies were included in the validation studies. Piroxicam was incorporated as internal standard. The limits of detection (LOD) and quantitation (LOQ) were calculated to be 0.1 µg/ml and 0.3 µg/ml, respectively. Acceptable level of linearity was studied over the range of 0.5-5µg/ml. However, three spiked concentrations (2, 3 and 4 µg/ml) were taken for accuracy and precision studies. The accuracy of Lornoxicam in human plasma was 89.63-100.4 %. After successful quantitation of Lornoxicam in human plasma, the study was aimed at comparing pharmacokinetics of newly formulated controlled release (CR) microparticles with branded immediate release (IR) tablet formulation of Lornoxicam. An open-label, two-period, randomized crossover study was conducted on 24 adult Pakistani male volunteers. After randomization, entitle subjects received single dose of Lornoxicam CR 16 mg capsule (test) and two doses (morning & evening) of Lornoxicam IR 8mg tablets (reference). Administration of formulations was repeated in alternate manner after a washout period of one week. Pharmacokinetic (PK) parameters were measured by Kinetica 5.0 using plasma concentration-time data. Peak plasma concentration (Cmax) was 12.8% lower for CR formulation when compared to IR formulation (270.9 ng/mL vs 339.44 ng/mL, respectively), time taken to attain Cmax (tmax) was 5.25 h versus 2.08 h respectively. Area under the time concentration (AUC) values for both CR and IR formulations were found comparable. The 90% CIs for the ln-transformed ratios of Cmax, AUC0-24, and AUC0-¥ were 87.21%, 108.51%, and 102.74%, respectively and were within pre-defined bioequivalence range (80%-125%). The findings suggested that CR formulation of Lornoxicam did not change the overall pharmacokinetic properties of Lornoxicam in terms of rate and extent of absorption. Both formulations demonstrated good tolerability in enrolled subjects. In the continuation of this research work, the potential of modified emulsion solvent evaporation method (MESE) was effectively utilized to formulate microparticles of Lornoxicam using Eudragit RS 100 and HPMC either alone or in combination. The resulting multiparticulate system was studied for micromeritic properties and drug loading. In addition, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) were applied to characterize morphology and compatibility. In-vitro drug release was studied by pH change method i.e 0.1 N HCl as dissolution medium for first 2 hours and in phosphate buffer of pH 6.8 for 22 hours. The microparticles obtained were yellowish in colour and had good flow properties. In this case, encapsulation efficiencies ranged from 70.52% ± 1.65 to 89.04% ± 1.26. The drug polymer compatibility studies confirmed the stable nature of Lornoxicam in the prepared microspheres. SEM findings showed that the microparticles were round to oval in shape. Dissolution studies showed sustained in-vitro drug release determined by increasing contents of Eudragit RS 100. Highest retardation in drug release occurred at co-polymer ratio of 1:3 in which amount of drug maximally released was 72.92% ± 3.29. The mechanism of drug release was governed by diffusion and anomalous mechanisms as depicted by „n‟ value which varied from 0.331 to 0.595. Of the six microparticulate batches of Lornoxicam fabricated by modified emulsion solvent evaporation method, in-vitro-in-vivo (IVIVC) characterization of four different sustained-release Lornoxicam tabletted microparticles (BF-1, BF-2, BF-4 and BF-6) and control immediate release tablet (Xika Rapid®8 mg, Hilton Pharma) was performed. In vitro characterization included dissolution study, SEM analysis and FTIR spectroscopy. As previously described, a validated method developed by HPLC procedure was used to analyze the results of bioavailability studies conducted on twenty healthy volunteers. After that, level A in vitro-in vivo correlation developed between the percent drug dissolved (in vitro) and the percent drug absorbed (in vivo) data of optimized formulations showed good linear correlation values (R2 = 0.953, 0.9321, 0.9896 for BF4, BF6 and control formulations, respectively) at specific time points. However, BF4 is comparatively closer to the control formulation that shows a reliable prediction of the plasma concentrations obtained following a single dose of lornoxicam controlled release formulation