The objective was to investigate the suitable polymeric films for the development of diltiazem hydrochloride (diltiazem HCl) transdermal drug delivery systems. Hydroxypropyl methylcellulose (HPMC) and ethylcellulose (EC) were used as hydrophilic and hydrophobic film formers, respectively. Effects of HPMC/EC ratios and plasticizers on mechanical properties of free films were studied. Effects of HPMC/EC ratios on moisture uptake, in vitro release and permeation through pig ear skin of diltiazem HCl films were evaluated. Influence of enhancers including isopropyl myristate (IPM), isopropyl palmitate (IPP), N-methyl-2-pyrrolidone, oleic acid, polyethylene glycol 400, propylene glycol, and Tween80 on permeation was evaluated. It was found that addition of EC into HPMC film produced lower ultimate tensile strength, percent elongation at break and Young's modulus, however, addition of EC up to 60% resulted in too hard film. Plasticization with dibutyl phthalate (DBP) produced higher strength but lower elongation as compared to triethyl citrate. The moisture uptake and initial release rates (0-1 h) of diltiazem HCl films decreased with increasing the EC ratio. Diltiazem HCl films (10:0, 8:2 and 6:4 HPMC/EC) were studied for permeation because of the higher release rate. The 10:0 and 8:2 HPMC/EC films showed the comparable permeation-time profiles, and had higher flux values and shorter lag time as compared to 6:4 HPMC/EC film. Addition of IPM, IPP or Tween80 could enhance the fluxes for approx. three times while Tween80 also shorten the lag time. In conclusion, the film composed of 8:2 HPMC/EC, 30% DBP and 10% IPM, IPP or Tween80 loaded with 25% diltiazem HCl should be selected for manufacturing transdermal patch by using a suitable adhesive layer and backing membrane. Further in vitro permeation and in vivo performance studies are required.

Stress affects the male reproductive system and can cause sub-fertility or infertility. Although Phyllanthus emblica L. (PE) extract has been shown to have high antioxidant capacity and protective properties in damaged tissue, the preventive effects of PE extract on testicular function from stress-related impairment have never been demonstrated. This study aimed to investigate the effects of PE aqueous leaf extract on testicular impairment and protein marker changes in rats suffering from chronic stress. Adult male rats were divided into four groups: a control group, a chronic stress (CS) group, and two groups with CS that received different doses of PE extract (50 or 100 mg/kg body weight (BW)). In the treatment groups, the animals were given PE extract daily before stress induction for 42 consecutive days. Stress was induced through immobilization (4 h/d) followed by forced cold swimming (15 min/d). Sperm quality and the histology of the testes and caudal epididymis were examined, as were levels of serum corticosterone, testosterone, and malondialdehyde (MDA). The expressions of testicular steroidogenic acute regulatory (StAR) and tyrosine-phosphorylated proteins were investigated using immuno-Western blot analysis, as these proteins are assumed to play important roles in spermatogenesis and androgen synthesis. The results showed that PE (50 mg/kg BW) significantly increased sperm concentration and testosterone levels, while decreasing corticosterone levels, MDA levels, sperm head abnormalities, and acrosome-reacted sperm in CS rats. In addition, PE at both doses was found to diminish testicular histopathology in the CS rats. We also found that 50 mg/kg BW of PE significantly improved StAR protein expression and altered the intensities of some tyrosine-phosphorylated proteins in testis. We conclude that PE leaf extract at 50 mg/kg BW can prevent testicular damage in rats with CS.

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Objective: The objectives of this study were to prepare and characterize a buccal mucoadhesive patch using poly (vinyl alcohol) (PVA), poly (vinyl pyrrolidone) (PVP) as a mucoadhesive matrix, Eudragit S100 as a backing layer, and lidocaine HCl as a model drug.Methods: Lidocaine HCl buccal patches were prepared using double casting technique. Molecular interactions in the polymer matrices were studied using attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC) and X-ray diffractometry. Mechanical and mucoadhesive properties were measured using texture analyzer. In vitro permeation of lidocaine HCl from the patch was conducted using Franz diffusion cell.Results: Both of the free and lidocaine HCl patches were smooth and transparent, with good flexibility and strength. ATR-FTIR, DSC and X-ray diffractometry studies confirmed the interaction of PVA and PVP. Mechanical properties of matrices containing 60% PVP were significantly lower than those containing 20% PVP (*P<0.05). Mucoadhesive properties had a tendency to decrease with the concentration of PVP in the patch. The patch containing 60% PVP had significantly lower muco-adhesiveness than those containing 20% PVP (*P<0.05). In vitro permeation revealed that the pattern of lidocaine HCl permeation started with an initial fast permeation, followed by a slower permeation rate. The initial permeation fluxes follow the zero-order model of which rate was not affected by the PVP concentrations in the PVA/PVP matrix. Conclusion:Mucoadhesive buccal patches fabricated with PVA/PVP were successfully prepared. Incorporation of PVP in PVA/PVP matrix affected the strength of polymeric matrix and mucoadhesive property of patches.