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Transdermal drug delivery has attracted much attention as an alternative to intravenous and oral methods of delivery. But the main barrier is stratum corneum. Terpenes classes of chemical enhancers are used in transdermal formulations for facilitating penetration of drugs. The aim of the study is to evaluate terpenes as skin penetration enhancers and correlate its relationship with permeation and lipophilicity. In this study, alfuzosin hydrochloride (AH) hydrogels were prepared with terpenes using Taguchi orthogonal array experimental design. The formulations contained one of eight terpenes, based on their lipophilicity (log P 2.13-5.36). The percutaneous permeation was studied in rat skin using diffusion cell technique. Flux, cumulative amount, lag time and skin content of AH were measured over 24 hours and compared with control gels. Nerolidol with highest lipophilicity (log P 5.36 ± 0.38) showed highest cumulative amount (Q24) of 647.29 ± 18.76 μg/cm2 and fluxrateof 28.16 ± 0.64 μg/cm2/hour. It showed decreased lag time of 0.76 ± 0.15 hours. Fenchone (2.5%) (log P 2.13 ± 0.30) produced the longest lag time 4.8 ± 0.20 hours. The rank order of enhancement effect was shown as nerolidol > farnesol > limonene > linalool > geraniol > carvone > fenchone > menthol. Lowest skin content was seen with carvone. Increase in lipophilicity of terpenes showed increase in flux, cumulative amount (Q24), and enhancement ratio which was significant with P < 0.000. But lag time was decreased and no correlation was found between lipophilicity and skin content. Histological studies showed changes in dermis which can be attributed to disruption of lipid packing of stratum corneum due to effect of nerolidol within lipid lamellae. It was found that small alcoholic terpenes with high degree of unsaturation enhance permeation of hydrophilic drugs, liquid terpenes enhance better than solid terpenes and terpenes with high lipophilicity are good penetration enhancers.

The objective of the present study is to explore the efficient chemical penetration enhancer among the various enhancers available in overcoming the stratum corneum barrier in transdermal delivery of Alfuzosin hydrochloride (AH). The different enhancers were incorporated in 2% Carbopol gel which was selected as a control and evaluated by in vitro diffusion studies through dialysis membrane and permeation through the rat abdominal skin using Keshary-Chien diffusion cells. All the enhancers increased the release rate through the dialysis membrane when compared with control except oleic acid which decreased the release rate but showed maximum solubility of the drug. Among the various enhancers Transcutol 20% and tween-20 (2%) showed the highest cumulative amount (Q 24) of 702.28 ± 6.97 μg/cm2 and 702.74 ± 7.49 μg/cm2, respectively. A flux rate of 31.08 ± 0.21 μg/cm2/hr by Transcutol 20% and 30.38 ± 0.18 μg/cm2/hr by tween-20 (2%) was obtained. Transcutol 20% showed decreased lag time of 0.13 ± 0.05 hr. The lowest skin content of 342.33 ± 5.30 μg/gm was seen with oleic acid 2.5%. Maximum enhancement of flux by 3.94-fold was obtained with transcutol 20%. Primary skin irritation studies were performed with rabbit. Histopathological studies of transcutol 20% showed marked changes such as degeneration and infiltration of mononuclear cells in dermis indicating the effect of transcutol on the skin. Among the different enhancers transcutol is efficient in enhancing transdermal delivery of AH.

In the present investigation efficiency of ethosomes as novel lipid carriers for transdermal delivery of Alfuzosin Hydrochloride (AH) has been evaluated. Taguchi robust design method was used for optimization of ethosomal formulations. Phospholipid type, concentration of phospholipid and concentration of ethanol was selected as independent variables and their effect on the dependent variables (entrapment efficiency and flux) was studied. Ethosomal formulation (EA8) with soya phosphatidylcholine (3%) and ethanol 20% were optimized. Vesicles were spherical, unilamellar with smooth surface. The optimized formulation exhibited vesicle size (6.85 ± 1.35µm), zeta potential (-8.14 ± 0.62mv), entrapment efficiency (91.86 ± 3.25%), flux (27.42 ± 0.04µg/cm2/hr), lag time (0.26±0.20hr) and skin deposition (298.01 ± 15.4µg/g). Transdermal flux was enhanced by 6.92 times over drug solution. Vesicle skin interaction studies showed fatty change in the dermis. The formulations were stable at 4°C for 120 days. Results suggested ethosomes as efficient carriers for AH transdermal delivery.DOI: http://dx.doi.org/10.3329/icpj.v1i11.12063 International Current Pharmaceutical Journal 2012, 1(11): 370-375

The most common and improved bioavailable route for protein and peptide drugs is injectable route. These drugs are generally preferred to give in invasive route to get high bioavailability though possessing disadvantages and the major one is patient non-compliance. Hence, various non-invasive route of administration has been under research for these drugs to fetch more advantages. Although bioavailability is a major problem with non-invasive route such as oral, nasal, ocular, transdermal, rectal, colon, and vaginal route, these routes have been preferred compared to existing invasive one. Many researches have been conducted in this area, but achieving success is significantly challenging. The nasal delivery has been successfully exploited for vaccines compare to all other non-invasive drug delivery system. Currently, only molecule to reach market is oral cyclosporine. The present review aims to discuss the potential non-invasive routes of protein and peptide drug delivery. The factors which will affect drug permeation, and the bioavailability of proteins administered through these routes is also emphasized.

Objective: The present research work unearthed not only pharmacognostic features of the seeds of Trichosanthes cucumerina but also the nephroprotective activity of 60% hydro alcoholic extract against Cisplatin-induced Wistar rat model. Materials and methods: Present study dealt with the detailed pharmacognostic study of the seeds of Trichosanthes cucumerina. 60% hydro alcoholic extract was prepared by hot extraction method. Preliminary phytochemical screening was carried out. Based on acute toxicity studies nephroprotective effect of the extract was screened at 200 and 400 mg/kg, b. w. in curative and prophylactic regimen. Nephrotoxicity was induced in male Wistar rats by administration of Cisplatin (5mg/kg, b.w. i.p. as a single dose). Nephroprotective activity was assessed by estimating serum markers and urinary functional parameters supported by anti-oxidant studies and histopathological aspects. Results: Microscopic studies showed that the seed coat had outer aerenchymatous tissue, inner parenchymatous tissue and innermost compact lines of sclereids. Physicochemical evaluation yielded alcohol and water soluble extractive values of 20.8 and 8.05%w/w. Total ash, acid insoluble and water soluble ash values were 7.15, 6.45 and 0.5 respectively. Fluorescence analysis imparted characteristic colours to the seed powder when observed under visible and UV light. Cisplatin-induced nephrotoxicity was indicated by increased levels of serum markers and urinary functional parameters which were reversed by the extract in dose dependent manner. The results were substantiated by anti-oxidant studies and histopathological studies. Conclusion: Various pharmacognostic parameters evaluated assisted in identification and standardization of seeds of Trichosanthes cucumerina in crude form. Present study revealed that hydroalcoholic extract attenuated the nephrotoxicity and provided the strengthened scientific evidence for the use of seeds of Trichosanthes cucumerina in nephrotoxicity.

Transdermal drug delivery system (TDDS) shows promising results when compared with oral drug delivery system mainly by eliminating the first pass metabolism and by improving the bioavailability of drug. Hydrophilic gels are networks of polymer chains that are sometimes found as colloidal gels in which water is the dispersion medium. Ibuprofen, nonsteroidal anti-inflammatory drug used to relieve pain, reduces fever and anti-inflammation. The purpose of present research is to demonstrate the influence of various enhancers (transcutol and stearylamine) in various concentrations on percutaneous permeation of ibuprofen hydrophilic gel from HPMC K4M & HPMC K100M gel formulation. Gelling agents at various concentrations were preliminary screened for gel consistency. The control and the prepared gels were evaluated for clarity, homogeneity, spreadability, extrudability, drug content, invitro diffusion, ex-vivo permeation, skin irritation, anti-inflammatory activity and stability studies. All formulations have shown better physicochemical properties. Ex-vivo skin permeation studies reveals that the (IBU29) formulated using HPMC K4M 6%, transcutol 40% and stearylamine 4% as permeation enhancers has shown maximum drug release of 86.4 % for 24hrs. Permeability parameters like flux were found to be 1940.68±0.06µg/cm²/hr, permeability coefficient was found 31 ×10-3 cm/hr and Q24 was found to be 5240.82±0.06µg/cm² and enhancement ratio of 13.06 over pure drug. Skin irritation studies showed irritation potential of “0” score thus providing to be non-irritant. The anti-inflammation studies were performed with inflammation induced by carrageenan 1% w/v solution. Optimized formulation (IBU29) showed highest reduction of inflammation comparable to marketed preparation BRUGESIC GEL®. The formulations were stable at room temperature for 1 month.Key words: Transdermal gel, Ibuprofen, HPMC K4M, HPMC K100M, Penetration- enhancer..