Menstrual Cycle in Female Workers

Menstrual disorders are abnormalities that occur in the menstrual cycle. There are various menstrual disorders that women can experience, ranging from too little or too much menstrual blood, painful menstruation, to depression before menstruation or premenstrual dysphoric disorder. Physical activity is divided into three levels, namely light, moderate and heavy physical activity. Physical activity of heavy intensity can cause physiological disorders of the menstrual cycle. Presence of menstruation (amenorrhoea), thinning of the bones (osteoporosis), menstrual irregularities or intermenstrual bleeding, abnormal growth of the uterine wall, and infertility.

Comparative Study of Matrix Transdermal Patches of Metoprolol: in Vitro and in Vivo Characterization

Aim of present study was to development and evaluation of matrix patches of metoprolol tartrate containing enhancers for sustained and enhanced transdermal delivery. Ethyl cellulose (EC), poly vinyl pyrrolidone (PVP), eudragit RS 100 (ERS) and eudragit RL 100 (ERL) were used as film formers alone or in combination. Dibutyl phthalate was used as plasticizer. Patches were prepared by plate casting method. Polyvinyl alcohol was used to prepare backing membrane. Prepared polymeric matrix patches containing no enhancer were characterized for physical appearance, thickness, weight variation, moisture contents and moisture up take capacity. Fourier transform infrared (FTIR) spectroscopic studies of prepared patches were performed to identify any chemical and physical interaction between drug and excipients. In vitro drug release studies were carried out in phosphate buffer pH 7.4 by using paddle over disc method. Release mechanism was elucidated by subjecting the in vitro release data to kinetic analysis by using DDsolver ® excel based add in program. Scanning electron microscopy (SEM) was performed after release to further elaborate release process. In vitro permeation studies were performed on Franz diffusion cell by using excised rabbit skin. Three polymeric combinations i.e. EC-PVP, EC-ERL and ERS-ERL were selected for further incorporation of enhancers. Non-ionic surfactants i.e. Span 20, Span 60, Span 80, Span 85, Tween 20 and Tween 80 were incorporated in polymeric combination of EC and PVP as permeation enhancers in two concentrations of 5% and 10%. Combination of EC and ERL was used for preparation of matrix patches containing 10 % w/w of Isopropyl myristate (IPM), dimethyl sulphoxide (DMSO), span 20, tween 20 and eucalyptus oil as enhancers. Four different terpenes like eucalyptol, limonene, nerolidol and menthol were employed in polymeric combination of ERL and ERS, in concentrations of 5%, 10% and 15% w/w of polymer. Formulations were optimized after enhances addition. Patches after incorporation of enhancers were characterized for physical properties, FTIR and SEM analysis. In vitro release and permeation studies were carried out to compare effect of enhancers and their concentration on release. Selected patch formulations were subjected to in vivo studies by two periods, two treatments randomized, cross over design in rabbits (n =6) for pharmacokinetic comparison with oral solution administration. Skin irritation XXIstudies were performed on healthy volunteers for terpene containing patches by measuring level of erythema with Mexameter ® . In presence of non-ionic surfactants initial burst release of metoprolol from EC-PVP patches was increased. However, overall release was decreased due to improved physical appearance in presence of nonionic surfactants. Span 20 and Tween 20, which have saturated shorter fatty acid side chains, showed highest enhancement effect with 1.73 and 2.01 folds increase in permeation rate when compared to control, respectively. Incorporation of enhancers in patches of EC-ERL had not affected amount of drug release up to 24 hrs except that of formulation containing DMSO where fast release was observed. Highest permeation flux in EC-ERL patches was observed for formulation containing IPM with 2 fold enhancement in permeation. Permeation flux for patches was in order of control (with no enhancer) > IPM > Tween 20 > Span 20 > DMSO = eucalyptus oil. Results of in vitro permeation studies of patches containing terpenes showed that despite of decrease in drug release by incorporation of enhancers, there was increase in skin permeation of metoprolol. Release from patches was indirectly related to the lipophilicity of terpenes. Limonene was the most effective enhancer among the patches containing terpenes and enhancement effect of terpenes on metoprolol was in the rank order of limonene > menthol > nerolidol > eucalyptol. Enhancement effect was increased by increase in concentration of enhancer in all formulations. However, no direct linear relationship was observed between permeation rate and enhancer concentration. Pharmacokinetic analysis of in vivo data elucidated that application of Tween 20 containing transdermal patch increased systemic availability (1.13 fold) and prolonged half life (almost 10 times) of metoprolol tartrate in comparison to oral administration. Whereas no increase in metoprolol bioavailability was observed after IPM (10%) containing patch application but half life was increased 8 times when compared to oral administration. Limonene (15%) containing patch application exhibited 1.47 folds increase in bioavailability and t 1/2 was extended up to 16 times. Moreover, skin irritation studies in healthy volunteers revealed that metoprolol tartrate patches containing terpenes were well tolerated. XXIIIt can be concluded that tween 20, IPM and limonene can be successfully employed as efficient permeation enhancers for transdermal delivery of metoprolol tartrate from EC- PVP, EC-ERL and ERS-ERL matrix patches, respectively. Moreover, a single patch of metoprolol is capable to provide sustained continuous delivery of metoprolol for more than two days across skin. Thus application of metoprolol tartrate transdermal patches can be used as an alternative of oral route for the treatment of hypertension.