Formulation by design based risperidone nano soft lipid vesicle as a new strategy for enhanced transdermal drug delivery: In-vitro characterization, and in-vivo appraisal.

The present study was designed to formulate and optimize transdermal risperidone soft lipid vesicles. The formulation optimized with phospholipid, safranal and ethanol were incorporated as permeation and absorption enhancers. The optimized risperidone soft lipid vesicle was further evaluated for skin irritation study, in-vivo pharmacokinetic study and locomotor activity. Three factor three level Box-Behnken design (BBD) was used to statistically optimize soft lipid vesicle using safranal (A), ethanol (B)and phospholipid (C) as independent variable, while their effect was observed for vesicle size (Y1), entrapment efficiency (Y2) and flux (Y3). The optimized risperidone soft lipid vesicle (Ris-opt) showed nanometric vesicle size, high entrapment efficiency and marked enhancement in transdermal flux. The extent of absorption from Ris-opt was greater when compared to oral suspension with relative bioavailability of 177%. The histopathological evaluation revealed developed formulation did not showed skin irritation compared to standard irritant. The significant findings presented here encourage further studies with risperidone soft lipid vesicles for treatment of schizophrenia.

Brain Targeting of Temozolomide via the Intranasal Route Using Lipid-Based Nanoparticles: Brain Pharmacokinetic and Scintigraphic Analyses.

The aim of the present work was to investigate the efficacy of temozolomide nanostructured lipid carriers (TMZ-NLCs) to enhance brain targeting via nasal route administration. The formulation was optimized by applying a four-factor, three-level Box-Behnken design. The developed formulations and the functional relationships between their independent and dependent variables were observed. The independent variables used in the formulation were gelucire (X1), liquid lipid/total lipid (X2), Tween 80 (X3), and sonication time (X4), and their effects were observed with regard to size (Y1), % drug release (Y2), and drug loading (Y3). The optimized TMZ-NLC was further evaluated for its surface morphology as well as ex vivo permeation and in vivo studies. All TMZ-NLC formulations showed sizes in the nanometer range, with high drug loading and prolonged drug release. The optimized formulation (TMZ-NLCopt) showed an entrapment efficiency of 81.64 ± 3.71%, zeta potential of 15.21 ± 3.11 mV, and polydispersity index of less than 0.2. The enhancement ratio was found to be 2.32-fold that of the control formulation (TMZ-disp). In vivo studies in mice showed that the brain/blood ratio of TMZ-NLCopt was found to be significantly higher compared to that of TMZ-disp (intranasal, intravenous). Scintigraphy images of mouse brain showed the presence of a high concentration of TMZ. The AUC ratio of TMZ-NLCopt to TMZ-disp in the brain was the highest among the organs. The findings of this study substantiate the existence of a direct nose-to-brain delivery route for NLCs.

Nanoemulsion: for improved oral delivery of repaglinide.

Repaglinide (RPG) is a fast-acting prandial glucose regulator. It acts by stimulating insulin release from pancreatic ß-cells. Recurrent dosing of RPG before each meal is burdensome remedy. Hence the plan of the present study was to evaluate nanoemulsion as a hopeful carrier for RPG for persistent hypoglycemic effect. The drug was incorporated into oil phase of nanoemulsion to give improved biopharmaceutical properties as compared to the lipid-based systems. Pseudo ternary phase diagrams were prepared by aqueous titration method. Formulations were selected at a difference of 5% w/w of oil from the o/w nanoemulsion region of phase diagrams. The optimized nanoemulsion formulation constituted sefsol-218 (5% v/v) as an oil phase, 30% v/v of Tween-80 and transcutol as a surfactant and co-surfactant to restrain nanodroplet size and low viscosity and distilled water (65%). In vitro dissolution studies showed higher drug release (98.22%), finest droplet size (76.23 nm), slightest polydispersity value (0.183), least viscosity (21.45 cps) and immeasurable dilution capability from the nanoemulsion as compared with existing oral tablet formulation. The optimized RPG nanoemulsion formulation showed better hypoglycemic effect in comparison to tablet formulation in experimental diabetic rats. No significant variations were also observed in the optimized formulation when subjected to accelerated stability study at different temperature and relative humidity over a period of 3 months.

Carvedilol nano lipid carriers: formulation, characterization and in-vivo evaluation.

The purpose of this study was to develop Carvedilol nanostructured lipid carriers (CAR-NLCs) using stearic acid and oleic acid as lipid, and to estimate the potential as oral delivery system for poorly water soluble drug. The particle-size analysis revealed that all the developed formulations were within the nanometer range. The EE and loading were found to be between 69.45-88.56% and 9.58-12.56%, respectively. The CAR-NLCopt showed spherical morphology with smooth surface under transmission electron microscope (TEM). The crystallization of the drug in NLC was investigated by powder X-ray diffraction and differential scanning calorimetry (DSC) and revealed that the drug was in an amorphous state in the NLC matrix. The ex vivo gut permeation study showed many folds increment in the permeation of CAR-NLCs compared to Carvedilol suspension (CAR-S). The oral bioavailability study of CAR was carried out using Wistar rats and relative bioavailability of CAR-NLCopt was found to be 3.95 fold increased in comparison with CAR-S. In vivo antihypertensive study in Wistar rats showed significant reduction in mean systolic BP by CAR-NLCopt vis-à-vis CAR-S (p < 0.05) owing to the drug absorption through lymphatic pathways. In conclusion, the NLC formulation remarkably improved the oral bioavailability of CAR and demonstrated a promising perspective for oral delivery of poorly water-soluble drugs. The promising findings in this investigation suggest the practicability of these systems for the enhancement of bioavailability of CAR.

In vitro and preclinical assessment of factorial design based nanoethosomes transgel formulation of an opioid analgesic.

CONTEXT: Tramadol is a centrally acting analgesic and requires frequent dosing. Hence, judicious selection of retarding formulations is necessary. Transdermal ethosomal gel delivery has been recognized as an alternative route to oral delivery. OBJECTIVE: The objective was to develop statistically optimized ethosomal systems for enhanced transdermal activity of tramadol vis-à-vis traditional liposomes. MATERIALS AND METHODS: Box-Behnken design was employed for optimization of nanoethosomes using phospholipon 90G (A), ethanol (B), and sonication time (C) as independent variables while dependent variables were the vesicle size (Y1), entrapment efficiency (Y2), and flux (Y3). It was prepared by rotary evaporation method and characterized for various parameters including entrapment efficiency, size and transflux. Preclinical assessments were conducted on Wistar rats to measure the performance of developed formulations. RESULTS: The optimized formulation provided mean vesicles size, reasonable entrapment efficiency and enhanced flux when compared with liposome (control). In-vivo absorption study showed a significant increase in bioavailability (7.51 times) compared with oral tramadol. The average primary irritancy index was found to be 1.4, indicating it to be non-irritant and safe for use. DISCUSSION AND CONCLUSION: The results also demonstrated that encapsulated tramadol increases its biological activity due to the superior skin penetration potential. The preclinical study indicates a significant (P < 0.05) extended analgesic effect compared to oral solution using the hot plate test method. The overall results suggest that developed formulation is an efficient carrier for transdermal delivery of tramadol.

QbD-based carbopol transgel formulation: characterization, pharmacokinetic assessment and therapeutic efficacy in diabetes.

In order to develop transdermal drug delivery system that facilitates the skin permeation of Pioglitazone (PZ) encapsulated in carbopol-based transgel system (proniosomes/niosome). The developed formulations were optimized using quality by design (QbD) approach and particle size, percentage entrapment and transdermal flux were determined. It was found to be more efficient delivery carriers with high encapsulation and enhanced flux value demonstrated that the permeation of PZ through skin was significantly increased with developed formulation. The transdermal enhancement from proniosome was 3.16 times higher than that of PZ from control formulation (ethanol buffer formulation, 3:7), which was further confirmed by confocal laser scanning microscopy. In vivo pharmacokinetic study of carbopol transgel showed a significant increase in bioavailability (2.26 times) compared with tablet formulation. It also showed better antidiabetic activity in comparison to marketed tablet, so our results suggest that carbopol-based transgel are an efficient carrier for delivery of pioglitazone through skin.

Enhanced transdermal delivery of luteolin via non-ionic surfactant-based vesicle: quality evaluation and anti-arthritic assessment.

Luteolin (LUT) is a promising molecule with potential anti-arthritic activity. This investigation presents formulation and evaluation of niosomal transgel for enhanced transdermal delivery of LUT. Different non-ionic surfactants and vesicle compositions were employed for preparation of niosomes. The vesicle size analysis showed that all vesicles were in the range from 534.58 to 810.22 nm which favoured efficient transdermal delivery. The entrapment of LUT in vesicle was found to be higher in all surfactant. The developed formulation was proved significantly superior in terms of amount of drug permeation with an enhancement ratio of 2.66 when compared to a control formulation. The in vivo bioactivity studies revealed that the prepared niotransgel formulation of LUT was able to provide good anti-arthritic activity and the results were comparable to standard (diclofenac gel for anti-arthritic and analgesic). Finally, the results were confirmed through radiological analysis which proved that the prepared niotransgel was effectively able to treat arthritis and results were comparable with the standard formulation.

Nanostructured lipid carriers of pioglitazone for transdermal application: from experimental design to bioactivity detail.

Pioglitazone (PZ) an anti-hyperglycemic agent is used in the treatment of type 2 diabetes. The aim of this study was to design PZ-loaded nanostructured lipid carriers (NLC) to investigate the bioavailability improvement by transdermal delivery. PZ NLCs were prepared using high-pressure homogenization followed by ultrasonication. The NLCs were evaluated for particle size analysis, drug loading, ex vivo skin transport studies and in vivo bioactivity study. The prepared NLCs had a mean size of 166.05 nm and drug loading of 10.41% with flux value of 47.36 µg/cm(2)/h. The entrapment of PZ is >70% in the NLCs with enhancement ratio of 3.2 times. The in vivo pharmacokinetic study showed 2.17 times enhancement in bioavailability study and pharmacodynamics study showed that PZ NLC-based transdermal therapeutic system (PNLG-TTS) lowers blood sugar level in a sustained pattern for a prolonged period of time as compared to Piosys tablet (marketed). The shelf life of the optimized formulation was found to be 1.83 years. These results clearly provide a lead that above NLCs-based TTS is potential controlled release formulation for PZ and could be a promising drug delivery system for the treatment of diabetes.

Development and evaluation of a novel in situ gel of sparfloxacin for sustained ocular drug delivery: in vitro and ex vivo characterization.

Conventional eye drops are the most popular delivery systems in the treatment of various eye infections. However, the major problem encountered in these dosage forms is precorneal elimination of the drug, resulting in poor bioavailability and therapeutic response. To overcome the side effects of pulsed dosing, an attempt has been made to formulate and evaluate a novel in situ gelling system of Sparfloxacin for sustained ocular drug delivery (ion and pH triggered gelling system). These gelling systems involve the use of sodium alginate (ion sensitive polymer) used as gelling agent and methylcellulose as viscosity-enhancing agent. The developed formulations were evaluated for clarity, pH, gelling capacity, rheological study, in vitro release study, ex vivo corneal permeation study, ocular irritation studies (HET-CAM test) and histopathological study using isolated goat corneas. The formulations were found to be stable, non-irritant and showed sustained release of the drug for a period up to 24 h with no ocular damage. In situ gel of sparfloxacin could be prepared successfully promising their use in ophthalmic delivery.

Novel carbopol-based transfersomal gel of 5-fluorouracil for skin cancer treatment: in vitro characterization and in vivo study.

5-fluorouracil (5-Fu) is an antineoplastic drug, topically used for the treatment of actinic keratosis and nonmelanoma skin cancer. It shows poor percutaneous permeation through the conventionally applicable creams and thus inefficient for the treatment of deep-seated skin cancer. In the present article, transfersomal gel containing 5-Fu was investigated for the treatment of skin cancer. Different formulation of tranfersomes was prepared using Tween-80 and Span-80 as edge activators. The vesicles were characterized for particle size, shape, entrapment efficiency, deformability and in vitro skin permeation. Optimized formulation was incorporated into 1% carbopol 940 gel and evaluated for efficacy in the treatment of skin cancer. 5-Fu-loaded transfersomes (TT-2) has the size of 266.9 ± 2.04 nm with 69.2 ± 0.98% entrapment efficiency and highest deformability index of 27.8 ± 1.08. Formulation TT-2 showed maximum skin deposition (81.3%) and comparable transdermal flux of 21.46 µg/cm(2) h. The TT-2-loaded gel showed better skin penetration and skin deposition of the drug than the marketed formulation. Composition of the transfersomal gel has been proved nonirritant to the skin. We concluded that the developed 5-Fu-loaded transfersomal gel improves the skin absorption of 5-Fu and provide a better treatment for skin cancer.

Formulation by design-based proniosome for accentuated transdermal delivery of risperidone: in vitro characterization and in vivo pharmacokinetic study.

AIM: The aim of this work was to investigate the effects of formulation variables on the development of risperidone proniosomal formulations as potential transdermal delivery systems. MATERIALS AND METHODS: A 43 factorial design was employed to evaluate individual and combined effects of formulation variables cholesterol (X1), span 60 (X2), phospholipid G90 (X3), and risperidone (X4) added on vesicle size (Y1), encapsulation efficiency (Y2), and flux (Y3) of proniosomes. RESULTS AND DISCUSSION: The investigated risperidone-loaded proniosomal formulation shows significantly higher skin permeation in comparison to conventional liposomes with ER of 4.4 times through rat skin. The bioavailability studies in rats indicated that mean value of AUC0-48 by ROPF-TTS was 1.31 times higher than that of oral dosage form. So it could be concluded that Cmax value of ROPF-TTS was significantly reduced while AUC values were apparently increased. CONCLUSION: The developed proniosomal-based transdermal therapeutic systems incorporating risperidone would provide a useful strategy for better management of schizophrenia.

Nanoparticles laden in situ gel for sustained ocular drug delivery.

Proper availability of drug on to corneal surface is a challenging task. However, due to ocular physiological barriers, conventional eye drops display poor ocular bioavailability of drugs (< 1%). To improve precorneal residence time and ocular penetration, earlier our group developed and evaluated in situ gel and nanoparticles for ocular delivery. In interest to evaluate the combined effect of in situ gel and nanoparticles on ocular retention, we combined them. We are the first to term this combination as "nanoparticle laden in situ gel", that is, poly lactic co glycolic acid nanoparticle incorporated in chitosan in situ gel for sparfloxacin ophthalmic delivery. The formulation was tested for various physicochemical properties. It showed gelation pH near pH 7.2. The observation of acquired gamma camera images showed good retention over the entire precorneal area for sparfloxacin nanoparticle laden in situ gel (SNG) as compared to marketed formulation. SNG formulation cleared at a very slow rate and remained at corneal surface for longer duration as no radioactivity was observed in systemic circulation. The developed formulation was found to be better in combination and can go up to the clinical evaluation and application.

A validated RP-HPLC method for simultaneous determination of propranolol and valsartan in bulk drug and gel formulation.

OBJECTIVE: A simple, precise, and stability indicating high performance liquid chromatography (HPLC) method was developed and validated for the simultaneous determination of propranolol hydrochloride and valsartan in pharmaceutical dosage form. MATERIALS AND METHODS: The method involves the use of easily available inexpensive laboratory reagents. The separation was achieved on Hypersil ODS C-18 column (250*4.6 mm, i.d., 5 µm particle size) with isocratic flow with UV detector. The mobile phase at a flow rate of 1.0 mL/min consisted of acetonitrile, methanol, and 0.01 M disodium hydrogen phosphate (pH 3.5) in the ratio of 50:35:15 v/v. RESULTS: A linear response was observed over the concentration range 5-50 µg/mL of propranolol and the concentration range 4-32 µg/mL of valsartan. Limit of detection and limit of quantitation for propranolol were 0.27 µg/mL and 0.85 µg/mL, and for valsartan were 0.45 µg/mL and 1.39 µg/mL, respectively. The method was successfully validated in accordance to ICH guidelines acceptance criteria for linearity, accuracy, precision, specificity, robustness. CONCLUSION: The analysis concluded that the method was selective for simultaneous estimation of propranolol and valsartan can be potentially used for the estimation of these drugs in combined dosage form.

Hippocratic oath and conversion of ethico-regulatory aspects onto doctors as a physician, private individual and a clinical investigator.

Hippocratic Oath is a living document for ethical conduct of the physicians around the world. World Medical Association has been amending the oath as per the contemporary times. Although physicians maintain their ethical standards while treating a patient yet many a times social, administrative and ruling powers either use physicians as their tool of oppression or victimize them for conducting duties as per their oath. The Tuskegee Syphilis Study and Human Radiation Experiments in America, Nazi Experiments in Germany and compulsory sterilization program in India were the studies where States used physicians for the advancement of their rationality or belief. Conversely victimization of physicians in Kosovo, Sri Lanka and incarcerating physicians for treating human immunodeficiency virus/acquired immunodeficiency syndrome patients in some countries is concerning. The Nuremberg code, the Declaration of Geneva, Belmont Report and Declaration of Helsinki are ethical documents while active involvement of Food and Drug Administration through "common rule" resulted in guidelines like International Conference on Harmonization and Good Clinical Practices. Still unethical studies are found in developing countries. Studies such as experimental anticancer drugs in 24 cancer patients without adequate prior animal testing and informed consent in Kerala, studies at All India Institute of Medical Sciences in New Delhi resulted in 49 deaths of children and many more suspicious studies are rampant. Reverting back to the fundamentals of the medical profession; teaching medical ethics and enforcement of "medical neutrality" by embarking some grade of "medical immunity" on the basis of the oath is necessary for ethical conduct of physicians.

Contact lenses in ocular therapeutics.

Drug delivery is a difficult task in the field of ocular therapeutics. Owing to the physiological and anatomical constraints of the eye, it is difficult to obtain the correct therapeutic concentration of a drug at the required site of action. This has led to clinicians recommending frequent dosing, which has resulted in noncompliance by patients and decreased cost effectiveness. To overcome these barriers, scientists have explored novel ocular delivery systems, such as in situ gels, ocuserts, nanoparticles and liposomes. A particularly novel form of such a delivery system are contact lenses, which are thin, curved plastic disks that are designed to cover the cornea and which cling to the surface of the eye owing to surface tension. In this article, we describe the introductory literature on ocular delivery using contact lenses, their classification and manufacturing process, and recent advances on drug delivery techniques using such lenses.

Monitoring of adverse drug reactions associated with antihypertensive medicines at a university teaching hospital in New Delhi.

AIM: To monitor the adverse drug reactions (ADRs) caused by antihypertensive medicines prescribed in a university teaching hospital. METHODS: The present work was an open, non-comparative, observational study conducted on hypertensive patients attending the Medicine OPD of Majeedia Hospital, Jamia Hamdard, New Delhi, India by conducting patient interviews and recording the data on ADR monitoring form as recommended by Central Drugs Standard Control Organization (CDSCO), Government of India. RESULTS: A total of 21 adverse drug reactions were observed in 192 hypertensive patients. Incidence of adverse drug reactions was found to be higher in patients more than 40 years in age, and females experienced more ADRs (n = 14, 7.29%) than males, 7 (3.64%). Combination therapy was associated with more number of adverse drug reactions (66.7%) as against monotherapy (33.3%). Calcium channel blockers were found to be the most frequently associated drugs with adverse drug reactions (n = 7), followed by diuretics (n = 5), and ß-blockers (n = 4). Among individual drugs, amlodipine was found to be the commonest drug associated with adverse drug reactions (n = 7), followed by torasemide (n = 3). Adverse drug reactions associated with central nervous system were found to be the most frequent (42.8%) followed by musculo-skeletal complaints (23.8%) and gastro-intestinal disorders (14.3%). CONCLUSIONS: The present pharmacovigilance study represents the adverse drug reaction profile of the antihypertensive medicines prescribed in our university teaching hospital. The above findings would be useful for physicians in rational prescribing. Calcium channel blockers were found to be the most frequently associated drugs with adverse drug reactions.

Formulation and optimization of nanotransfersomes using experimental design technique for accentuated transdermal delivery of valsartan.

The purpose of this work was to develop and statistically optimize nanotransfersomes for enhanced transdermal of valsartan vis-à-vis traditional liposomes. Nanotransfersomes bearing valsartan were prepared by conventional rotary evaporation method and characterized for various parameters including entrapment efficiency, vesicles shape, size, size distribution, and skin permeation. In vivo antihypertensive activity conducted on Wistar rats was also taken as a measure of performance of nanotransfersomes and liposomes. Nanotransfersomes proved significantly superior in terms of amount of drug permeated in the skin, with an enhancement ratio of 33.97 ± 1.25 when compared to rigid liposomes. This was further confirmed through a confocal laser scanning microscopy study. Nanotransfersomes showed better antihypertensive activity in comparison to liposomes by virtue of better permeation through Wistar rat skin. Finally, it could be concluded that the nanotransfersomes accentuates the transdermal flux of valsartan and could be used as a carrier for effective transdermal delivery of valsartan. FROM THE CLINICAL EDITOR: In this paper, the authors discuss the development and optimization of nanotransfersomes for enhanced transdermal of valsartan and demonstrate accentuated transdermal compared to standard preparations.

Role of novel terpenes in transcutaneous permeation of valsartan: effectiveness and mechanism of action.

CONTEXT: The greatest obstacle for transdermal delivery is the barrier property of the stratum corneum. Many approaches have been employed to breach the skin barrier; the most widely used one is that of chemical penetration enhancers. Of the penetration enhancers, terpenes are arguably the most highly advanced and proven category. OBJECTIVE: The aim of this investigation was to study effectiveness and mechanism of seven novel terpenes, namely iso-eucalyptol, ß-citronellene, valencene, rose oxide, safranal, lavandulol acetate, and prenol, as potential penetration enhancers for improved skin permeation of valsartan through rat skin and human cadaver skin (HCS) with reference to established terpene eucalyptol. METHODS: Skin permeation studies were carried out using Automated Transdermal Diffusion Cell Sampling System (SFDC 6, LOGAN Instruments Corp., NJ) on rat skin and HCS. The mechanism of skin permeation enhancement of valsartan by terpenes treatment was evaluated by Fourier transform infrared spectroscopy (FT-IR) analysis, differential scanning calorimetry (DSC) thermogram, and histopathological examination. RESULTS AND DISCUSSION: Among all study enhancers, iso-eucalyptol produced the maximum enhancement via rat skin [enhancement ratio (ER) = 7.4] and HCS (ER = 3.60) over control. FT-IR spectra and DSC thermogram of skin treated with aforesaid terpenes indicated that permeation occurred due to the disruption of lipid bilayers. No apparent skin irritation (erythema, edema) was observed on treatment with terpenes except ß-citronellene, safranal, lavandulol acetate, and prenol, which caused mild irritation. CONCLUSION: It is concluded that the iso-eucalyptol can be successfully used as safe and potential penetration enhancer for enhancement of skin permeation of lipophilic drug such as valsartan.

The emerging role of P-glycoprotein inhibitors in drug delivery: a patent review.

INTRODUCTION: The ATP-binding cassette superfamily contains membrane transporter proteins that transport a wide range of diverse compounds across cellular membranes. The P-glycoprotein (P-gp) is an important member of this family and a multi-specific drug efflux transporter that plays a significant role in governing the bioavailability of many clinically active drugs. The inhibition of this efflux transporter by various P-gp inhibitors forms a distinctive approach in improving bioavailability and conquering drug resistance. Most P-gp inhibitors exhibit limitations associated with their safety and unwanted pharmacokinetic interactions, thereby restraining their clinical applicability. AREAS COVERED: This review explores the investigations on the feasibility and applicability of various classes of P-gp inhibitors as described in recent patents for enhanced drug delivery. EXPERT OPINION: Several candidates presently under development look promising as P-gp inhibitors, e.g., tariquidar and elacridar. Pharmaceutical excipients currently constitute the most promising class of P-gp inhibitors and are considered safe and pharmaceutically acceptable for use in formulations. In addition, lipid-based excipients and thiolated polymers play an active role in affecting P-gp-mediated transport not only by altering the membrane fluidity or ATPase activity but by down regulating P-gp expression. An additional overture such as the prodrug derivatization of P-gp substrates is a feasible approach to bypass P-gp-mediated efflux.

Interactions between novel terpenes and main components of rat and human skin: mechanistic view for transdermal delivery of propranolol hydrochloride.

The purpose of this study was to investigate the effectiveness and mechanism(s) of percutaneous absorption of propranolol hydrochloride (PHCL) across rat and human cadaver skin using seven novel terpenes with reference to marker terpene 1,8-cineole. In-vitro skin permeation studies were carried out via rat and human skin models. The mechanism of skin permeation of PHCL by terpenes was evaluated by FTIR, DSC, activation energy measurement and histopathological examination. Amongst the new terpenes, 1,4-cineole was found to be most effective enhancer for diffusion of PHCL through rat skin (ER=3.07) and human cadaver skin (ER=2.42) as compared to control. FTIR spectra and DSC thermogram of skin treated with aforesaid terpenes indicated that permeation occurred due to the disruption of lipid bilayers. No apparent skin irritation (erythema, edema) was observed on treatment of skin with terpenes, the irritation was higher with the ß-citronellene and rose oxide. It was concluded that 1,4-cineole can be successfully used as potential permeation enhancer for PHCL. It enhanced the absorption of hydrophilic drug by extraction and disruption of lipid bilayers and keratin denaturation of stratum corneum.