An Empirical Analysis of Male Labour Force Participation in District Lahore

The present study examines the determinants of male labour force participation in district Lahore, Pakistan. The authors have collected data from age cohort 18-64 years by primary source. The results are tested by using logit model. The results show that age, increasing educational levels, parents’ level of education, presence of assets and marital status contribute significantly to higher male participation rate in the workforce.

Formulation and Evaluation of Tizanidine-Meloxicam Mucoadhesive Buccal Films by Central Composite Rotatable Design and Their Pharmacokinetic Studies

The current project was designed with the aim to extract arabinoxylan (ARX) from Ispaghula Husk followed by thiol modification to synthesize thiolated arabinoxylan (TARX) for mucoadhesive buccal films. Bi-layer buccal films for immediate release (IR) of Meloxicam (MLX) and sustained release (SR) of Tizanidine Hydrochloride (TZN HCl) were prepared. Different grades of hydroxypropyl methylcellulose (HPMC) were used as IR film former along with poly ethylene glycol (PEG 400) as a plasticizer. Mucoadhesive SR films were prepared by using ARX and TARX as a mucoadhesive SR film former along with glycerol as plasticizer. A statistical approach namely central composite rotatable design (CCRD) was applied to design and optimize the formulations. Alkali extraction method was used for ARX extraction, and later on synthesis of TARX was accomplished by esterification of ARX with thioglycolic acid (TGA) in the presence of HCl. ARX and synthesized TARX were evaluated for physicochemical characterization including micrometric properties, surface morphology, thermal behavior and crystallographic analysis. Albino rats were used for in-vivo safety analysis of both modified and unmodified polymers, which were further used for the preparation of SR films. Solvent casting technique was used for the fabrication of MLX containing IR films as well as TZN HCl containing SR films, subsequently subjected to physicochemical as well as mechanical characterization. Assays of the films were performed by high performance liquid chromatographic (HPLC) technique after successful development of validated HPLC methods in mobile phase as well as in rabbit’s plasma. A bilayer film was prepared by combining best formulation; each from IR (F5) and SR (F5) formulations for in-vivo analysis of MLX and TZN HCl by using Latin Square Crossover study design. Rabbits were used as experimental animals and pharmacokinetic parameters including, half-life (t1/2), maximum plasma concentration of the drugs (Cmax), time to reach Cmax (tmax) and area under the plasma concentration-time curve (AUC) were calculated. A noncompartmental model analysis by using PK-Solver software was applied for the calculation of stated pharmacokinetic parameters followed by statistical validation of the results with the help of analysis of variances (ANOVA) with 95% confidence interval applied by Graph Pad Prism ver.7.0.ARX was been successfully extracted from ispaghula husk with 39% of extraction yield. Thiolation of ARX was confirmed by the appearance of a characteristic peak at 2516 nm and presence of adequate amount of thiol contents i.e. 2809.003 ± 1.03 µmoles/g of the polymer. TARX flow properties were improved from poor to excellent category while x-ray difractometery (XRD) indicated slight proliferation of crystallinity from amorphous form. Safety studies conducted have proved both ARX and TARX were safe in the concentration range of 0.75 g/kg to 1.0 g/kg body weight. Potential of ARX and TARX as effective mucoadhesive drug retarding polymers were assessed and found to be an effective mucoadhesive and SR polymers up to 8 hrs, both in in-vitro drug release studies and in ex-vivo drug permeation studies. Drug release from ARX based optimized formulation was found to be 94%, while the amount of permeated drug through the buccal mucosa of the goat was 82%. Similarly, in case of TARX based SR films, 97% drug was released and 92.% was permeated across the buccal mucosa. Mucoadhesion of ARX was 1.59 ± 0.17 to 1.73 ± 0.11 N that was greatly improved up to 11.53 ± 0.17 N after modification of ARX into TARX. Both factors (polymer and plasticizer) showed constructive response as increase in their concentration found enhancing the mucoadhesion strength of the films. Selected IR film was found to be disintegrating in <15 sec, releasing more than 80% drug in initial 5min of dissolution studies and about 100% permeation of the drug in <30 min. Mobile phase was the mixture of methanol and doubled distilled water (8:2) with adjusted pH 3.0 utilized by high performance liquid chromatographic (HPLC) technique. Elution of the drugs was observed after injecting 20µl with flow rate of 0.8ml/min at an ambient temperature and 1400 psig pressure. Peaks of TZN HCl and MLX were observed with good resolution and symmetry at 2.69 min and 6.96 min retention times. Equivalent retention times were recorded for both drugs in rabbit’s plasma, suggesting the developed method as a suitable technique for the pharmacokinetic studies of the candidate drugs. After successful application of latin square cross over study design, it was evaluated that statistically significant improvement was observed in studied pharmacokinetic parameters when prepared formulations were compared with oral solutions of both drugs which were introduced as standards. In-vivo pharmacokinetics studies after administration of 1mg/kg of each drug, showed that Cmax for ARX based formulation was about 94 ng/ml while for TARX based formulation, it was approximately 105 ng/ml; suggesting significant difference in the Cmax of both formulations (p=0.0009) indicating better potential of TARX for bioavailability enhancement. Similarly, t1/2 of TZN HCl was momentously improved from 2.5 h to 9.4 h for F-ARX and 10.6 h for FTARX (p=0.0001). F-ARX and F-TARX showed in-significant tmax however, it was pointedly different from that of oral solution (p=0.0001). AUC of TZN HCl was diverse, not only for oral solution from F-ARX and F-TARX but also there was a significant variances between F-ARX and F-TARX (p=0.0009). Cmax of MLX was different from that obtained through oral solution to that acquired from F-ARX and FTARX (p=0.0141) and t1/2 of MLX from F-ARX was different significantly for MLX from oral solution (p=0.0192). However, tmax was non-significant for all three formulations of MLX.The research project was successfully conducted, achieving the goals of the synthesis of TARX and subsequently the development of bilayer buccal films. This was followed by effective demonstration of delivering the MLX and TZN HCl by placing in the buccal cavity. The study entails a promising scope in diverse areas. From the pharmacotherapeutic perspective it assures increased bioavailability and half-life of TZN HCl which otherwise might deteriorate in gastric environment. This is due to direct absorption of drug into blood circulation from buccal route, bypassing the hepatic fistpass effect and sustained property of the mucoadhesive polymer that allows slow release of the drug. From the pharmaco-economic viewpoint, this study identifies elements of cost effectiveness and patient compliance in a significant manner. Being lighter in weight and thickness, easy to use, easy to carry and attractive in appearance, this dosage form not only multiplies therapeutic effects at reduced cost but also enhance patient compliance by developing his interest in easy-to-take dosage form. In addition, the drugs i.e. MLX and TZN HCl, used to be delivered therapeutically by buccal film have proven synergistic effects, as reported by various studies. This phenomenon of synergism and IR property together with SR in this dosage form can be of significant value from pharmaceutical standpoint. Combination of drugs, belonging to diverse therapeutic classes, for diverse targeted pathophysiological conditions can definitely benefit greatly by means of this dosage form.