Biomedical subjects

Ramesh Panchagnula

Publications and source records attributed to Ramesh Panchagnula.

At least 37 records · Page 2Linked to original sources

PubMed2005

Single and multiple dose pharmacokinetic evaluation of a transdermal delivery system of imipramine hydrochloride.

The transdermal route provides an attractive alternative to the presently used peroral therapy with tricyclic antidepressants due to the avoidance of first-pass metabolism and the associated side effects. In this investigation an earlier developed transdermal delivery system (TDS) of imipramine hydrochloride (CAS 113-52-0; IMH) was evaluated with respect to dose proportionality at three different dose levels. Linearity was observed with the lower doses. For the prediction of in vivo plasma levels, various pharmacokinetic parameters such as alpha, beta, volume of distribution, and AUC0-infinity. were determined by single dose intravenous administration (2 mg/kg). The lowest dose was selected for the multiple dose study taking into consideration the issues of stability, safety, therapeutic range and linearity of pharmacokinetics. At all dose levels the experimental plasma values were significantly lower than predicted levels (p < 0.05) but 30-50 fold higher than the therapeutic range with no significant difference at different dose levels. The plasma levels obtained by repeated application were comparable to that obtained in the single dose study. In addition, IMH exhibited dose proportional pharmacokinetics at the higher doses (above 50 mg/day). The developed TDS was able to maintain steady-state plasma levels for the entire duration of the multiple dose study.

Administration, Cutaneous↗

PubMed2005

In vivo pharmacokinetic and tissue distribution studies in mice of alternative formulations for local and systemic delivery of Paclitaxel: gel, film, prodrug, liposomes and micelles.

The aim of this study was to increase the understanding on the pharmacokinetic and tissue distribution of paclitaxel as influenced by formulation approach. For this purpose, various formulations investigated in Swiss mice included liposomes, poloxamer 407 gel and chitosan film for subcutaneous route; and water-soluble methacrylate prodrug, liposomes and poloxamer micelles for systemic administration. During this study, the currently marketed formulation of Cremophor EL of paclitaxel was used as the reference. A highest plasma concentration following intravenous administration of paclitaxel was observed for rigid and 'Stealth((R))' liposomes containing the prodrug while, least was for covalently incorporated paclitaxel micelles. Further, poloxamer micelles demonstrated both the highest mean residence time of 7.34 h and volume of distribution (VSS=4.82 and VZ=5.87 L/kg) for paclitaxel. This was followed by prodrug loaded 'Stealth' liposomes, which showed a mean residence time of 4.96 h but were least distributed into apparent physiological volume (VSS=2.12 and VZ=3.16 L/kg). These results clearly signify the role of formulation/excipient in drug disposition and possible interactions. Importantly, due to decrease in the clearance rate of drug, the area under curve values of paclitaxel increased by 1.64- and 2.5-fold for micellar and prodrug loaded 'Stealth' liposomal formulations, respectively over reference formulation. While thermoreversible gels served to decrease plasma concentration of paclitaxel (8-fold) after subcutaneous administration, systemic levels were totally absent after implantation of films. In tissue distribution studies, maximum percent of paclitaxel was observed in liver for reference formulation, conventional liposomes and micelles whereas highest levels of prodrug and 'Stealth((R))' liposomes were in kidney and spleen, respectively. The novel formulations significantly altered tissue accumulation profiles of paclitaxel relative to the reference formulation, for example, reduction in uptake by heart from liposomes and micelles, as well as the major recognition mechanism for elimination. It is proposed that a combination therapy with liposomes and micelles of paclitaxel for systemic delivery along with implantation of chitosan film for local delivery, may serve not only to improve patient compliance by obliterating the need to administer Cremophor EL, but also increase patient survival.

Animals↗

PubMed2005

Preparation and characterization of water-soluble prodrug, liposomes and micelles of Paclitaxel.

Alternative formulations of paclitaxel were developed in order to improve its aqueous solubility, and characterized in vitro. A methacrylic acid based nanoconjugate of paclitaxel was synthesized by a simple esterification reaction with molecular weight of 1657 Da. The in vitro hydrolysis study on the prodrug of paclitaxel in presence of rat plasma has shown that the ester bond was quite stable (less than 1% of paclitaxel was liberated from prodrug in 24 h). This water-soluble prodrug was encapsulated into polyethylene glycol coated liposomes optimized with saturated lipids, to overcome the physical instability associated with paclitaxel. Under in vitro testing, prodrug liposomes seem very impressive with release of only 45% of payload in 180 h. Further, chemical as well as physical stability studies have shown that liposomes were stable without any signs of crystallization of paclitaxel. In addition, paclitaxel was covalently coupled to poloxamer via methacrylic acid linker to obtain a micelle forming conjugate. Evidence for self-assembly of this conjugate into micelles was provided by fluorescence spectroscopy, light scattering and differential scanning calorimetry techniques. Micellization of the conjugate was thermodynamically favored and the core of resulting micelles exhibited higher microviscosities (than poloxamer micelles). Release studies using dialysis technique along with high performance liquid chromatography revealed that paclitaxel is liberated from micelle in the form of methacrylic acid oligomer based prodrug in a gradual manner. These preliminary studies provided indication on the performance and feasibility of testing these carrier systems as a safer alternative to the Cremophor EL based paclitaxel formulation.

Animals↗

PubMed2004

Simultaneous determination of digoxin and permeability markers in rat in situ intestinal perfusion samples by RP-HPLC.

A simple, sensitive and specific reversed-phase high performance liquid chromatographic (RP-HPLC) assay for simultaneous determination of digoxin and permeability markers, in samples obtained from intestinal in situ single-pass perfusion studies, was developed and validated. Chromatography was carried on C-18 column with mobile phase comprising of acetate buffer (pH 3.0), acetonitrile and methanol in the ratio of 50:25:25 (v/v/v), was pumped at a flow rate of 0.5 ml/min and UV detection was employed at 220 nm. The average retention times for phenolred, propranolol, frusemide and digoxin were 9.1, 10.7, 12.9 and 15.3 min, respectively. The calibration curves were linear (R(2) > 0.998) in the range for each analyte. The method is specific and sensitive with limit of quantification of 25 ng/ml for digoxin and frusemide and 10 ng/ml for phenolred and propranolol. The method is accurate and precise with recoveries of digoxin in the range of 95.2 and 103.2% and relative standard deviation (R.S.D.) <5%. We found that this method was simple and reliable in permeability determination and to estimate the contribution of P-glycoprotein in limiting intestinal absorption.

Animals↗

PubMed2004

Dissolution test as a surrogate for quality evaluation of rifampicin containing fixed dose combination formulations.

The present investigation was aimed at developing a dissolution methodology to predict in vivo performance of rifampicin containing fixed dose combination (FDC) products. Six FDC formulations were used in this study, of which four had passed bioequivalence while two failed. Dissolution studies were conducted at agitation intensity of 30-100 rpm as a measure of hydrodynamic stress and at pH media corresponding to gastric and intestinal conditions. Formulations showed variable dissolution at different conditions and dissolution at 50 rpm was most sensitive and differentiated the release profiles of rifampicin under various pH conditions. It was possible to predict in vivo performance of rifampicin from FDCs when in vitro rate and extent of release at various pH was correlated with site, pH and concentration dependent absorption of rifampicin along with gastric emptying time. It was also seen that dissolution conditions recommended in USP for different types of FDCs were insensitive for the formulation changes. Based on this comprehensive evaluation, a decision tree is proposed which will act as a guideline for quality evaluation of FDC products and also will provide a fundamental knowledge for optimization of formulations failing in dissolution studies.

Biological Availability↗

PubMed2004

Development and characterization of biodegradable chitosan films for local delivery of Paclitaxel.

Intratumoral and local drug delivery strategies have gained momentum recently as a promising modality in cancer therapy. In order to deliver paclitaxel at the tumor site in therapeutically relevant concentrations, chitosan films were fabricated. Paclitaxel could be loaded at 31% wt/wt in films, which were translucent and flexible. Physicochemical characterization of paclitaxel via thermal, spectroscopic, x-ray diffraction, and electron microscopy techniques revealed information on solid-state properties of paclitaxel as well as chitosan in films. While chitosan was in amorphous form, paclitaxel seemed to be present in both amorphous and crystalline forms in film. The polymeric dispersion of paclitaxel in poloxamer formed fibrous structures generating discontinuities in the film matrix, thereby leading to the introduction of perturbations in the packing arrangement of polymer chains. These films released only 10% to 15% of loaded paclitaxel by a burst effect under in vitro testing conditions, with lysozyme having no effect on the release. However, films softened after implantation in mice and lost integrity over time. The implantable delivery system is not only biodegradable but also well tolerated in vivo and hence, biocompatible as revealed by histological studies. The lack of formulation-induced local inflammatory responses of paclitaxel chitosan films suggests a new paradigm for localized chemotherapy based on implantable systems.

Animals↗

PubMed2004

Reversed-phase liquid chromatography with ultraviolet detection for simultaneous quantitation of indinavir and propranolol from ex-vivo rat intestinal permeability studies.

A simple, rapid, sensitive and specific reversed-phase high performance liquid chromatographic (RP-HPLC) method involving ultraviolet detection (lambda = 210 nm) was developed for analysis of indinavir along with propranolol in samples obtained from ex vivo intestinal permeability studies. Chromatography was carried out on C-18 column with mobile phase comprising of phosphate buffer-acetonitrile (68:32, v/v) pumped at flow rate of 1 ml/min. The proposed method has a short run time of 12 min and involves a simple sample preparation for the purpose of reducing permeability model artifacts and to concentrate the samples. Fluorescein was used as internal standard. The proposed method has been validated with regard to specificity, detection limit, recovery, accuracy and precision. For both the drugs, method was found to be selective, linear (R(2) approximately 0.999), accurate (recovery = 100-105%) and precise (<3% R.S.D.) in the range of 2-20 microg/ml. The limit-of-detection and limit-of-quantification of the method were 40 ng/ml and 100 ng/ml for indinavir, and 30 and 80 ng/ml for propranolol, respectively. Indinavir, a widely prescribed HIV protease inhibitor, suffer from bioavailability problems where involvement of P-glycoprotein mediated drug efflux may play a significant role. The proposed method was successfully applied for intestinal permeability of indinavir to estimate the contribution of P-glycoprotein in limiting its oral bioavailability. The advantage of the developed method lies in the simultaneous determination of propranolol, a passive integrity marker, routinely employed in permeability studies and its selectivity in presence of various P-gp modulators and permeability markers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

Comparative bioavailability of rifampicin, isoniazid and pyrazinamide from a four drug fixed dose combination with separate formulations at the same dose levels.

Fixed dose combination (FDC) formulations became popular in the treatment of tuberculosis (TB) because of the better patient compliance, reduced risk of monotherapy and emergence of drug resistance in contrast to treatment with separate formulations of two to four first-line drugs. However, its successful implementation in national programs is limited by probable bioinequivalency of rifampicin if present in FDC form. In this regard, World Health Organization (WHO) and International Union Against Tuberculosis and Lung Disease (IUATLD) recommend FDCs only of proven bioavailability. Hence, bioequivalence study of four drug FDC tablet was conducted using 22 healthy male volunteers according to WHO recommended protocol to determine bioavailability of rifampicin, isoniazid and pyrazinamide compared to standard separate combination at the same dose level. The study was designed as two period, two treatment crossover experiment with a washout period of 1 week. Bioequivalence of rifampicin was estimated by plasma and urinary method for both rifampicin and its active metabolite, des-acetyl rifampicin whereas isoniazid and pyrazinamide were estimated from plasma. Mean concentration time profiles and all the pharmacokinetic parameters of rifampicin, isoniazid and pyrazinamide from FDC tablet were comparable to individual formulations and passed the bioequivalence test with power of the test above 95%. Further, bioequivalence of both rifampicin and isoniazid shows that in vitro interaction of rifampicin and isoniazid is clinically insignificant. Thus, it was concluded that FDC formulation is bioequivalent for rifampicin, isoniazid and pyrazinamide and ensures the successful treatment of TB without compromising therapeutic efficacy of any of these components of anti-TB therapy.

Administration, Oral↗

PubMed2004

Transdermal delivery of zidovudine: effect of terpenes and their mechanism of action.

The effect of various oxygen-containing monoterpenes such as cineole, menthol, alpha-terpineol, menthone, pulegone and carvone was investigated on ex vivo permeation of zidovudine (AZT) across rat skin. Furthermore, saturation solubility of AZT, its stratum corneum (SC)/vehicle partition coefficient and activation energy for diffusion across skin with or without terpene(s) in vehicle (66.6% ethanol in water) were determined to understand their mechanism of action. All the terpenes studied significantly increased transdermal flux of AZT in comparison to vehicle (p<0.05) and their enhancement activities are in the following decreasing order: cineole>menthol>menthone approximately pulegone approximately alpha-terpineol>carvone>vehiclewater. On the other hand, saturation solubility and SC/vehicle partition coefficient of AZT were not significantly altered (p>0.05) by terpenes. Activation energies of AZT permeation across rat skin from water, vehicle and cineole in vehicle were measured to be 20.4, 18.6 and 10.6 kcal/mol, respectively. Interactions between terpenes and SC lipids were studied with molecular modeling and found that terpenes form hydrogen bonds (bond lengths<2 A) with lipid head groups. The mechanism of permeation enhancement of AZT by terpenes was explained with thermodynamic activity, SC/vehicle partition coefficient, activation energy and molecular modeling studies.

Adjuvants, Pharmaceutic↗

PubMed2004

Biopharmaceutic and pharmacokinetic aspects of variable bioavailability of rifampicin.

Even today the treatment outcome of tuberculosis is questionable due to variable bioavailability of rifampicin, which was discovered four decades back. In this manuscript, results of bioequivalence trials reported are presented in the form of a figure that provides a comprehensive look at the rifampicin bioavailability literature, provides understanding of the problem and clears 'myths and assumptions' regarding rifampicin bioavailability from fixed-dose combination (FDC) formulations. It was found that FDCs of good as well as bad quality rifampicin containing formulations with reduced or increased relative bioavailability are available. In addition, 'rifampicin alone' formulations also show variability in bioavailability. In the context of anomalous bioavailability of rifampicin, reasons postulated in literature are summarized. Approaches needed to solve the issue of rifampicin bioavailability are discussed on the basis of LADMER and BCS.

Antibiotics, Antitubercular↗

PubMed2004

Pharmacokinetic evaluation of an azithromycin controlled release dosage form in healthy human volunteers: a single dose study.

Azithromycin (AZI) follows a two-compartment model pharmacokinetically. The purpose of this study was to evaluate the in vivo performance of a controlled release (CR) formulation of AZI, which would eliminate the risk of high peak plasma concentrations obtained within 2-3 h after peroral administration of immediate release (IR) products. The study was conducted in twelve healthy male human volunteers to compare an experimental NIPER product (CR tablets) with Vicon (IR tablets) at the same dose level as a single-dose, randomized, one-period, two-treatment, and parallel-study. Concentrations of AZI in serum samples were assessed using the validated HPLC method. From the serum concentration-time profiles various pharmacokinetic parameters (AUC(0-96), AUC(0-inf), C(max) and T(max)) were calculated for both products. Results showed that the high peak concentration obtained by administration of a conventional IR formulation were eliminated with the CR product. A mean dosage form index (DI) of 1.17 with fluctuations of 7.57% was obtained with the CR product at steady state level, indicating reduced fluctuations at the steady state serum concentrations. Elimination of the pronounced peak as well as fluctuations reduced or minimized AZI adverse effects associated with the IR product.

Administration, Oral↗

PubMed2004

Transdermal iontophoresis of insulin: IV. Influence of chemical enhancers.

Transdermal iontophoresis per se may not be able to achieve significant permeation of large peptides like insulin, thereby necessitating the use of combination strategies involving chemical enhancers and iontophoresis. The study investigated effect of pre-treatment with commonly used vehicles such as ethanol (EtOH), propylene glycol (PG), water and their binary combinations, dimethyl acetamide (DMA), 10% dimethyl acetamide in water, ethyl acetate (EtAc) and isopropyl myristate (IPM) on insulin iontophoresis. Solvents, which acted on the lipid bilayer, were able to produce a synergistic enhancement with iontophoresis. The binary solvent systems produced either additive or no effect, when combined with iontophoresis. FT-IR studies showed that EtOH, DMA, EtAc caused lipid extraction and the former two also caused changes in skin proteins, whereas IPM caused increase in lipid fluidity. TGA studies showed that EtOH and PG caused dehydration of skin. Skin barrier property was severely compromised with DMA, followed by EtOH and EtAc, while IPM and PG had relatively minimum skin barrier altering potential. Thus, this study demonstrates the possibility of achieving higher permeation of large peptides like insulin by combining iontophoresis with chemical enhancers that act on the intercellular lipids.

Adjuvants, Pharmaceutic↗

PubMed2004

Transdermal delivery system for zidovudine: in vitro, ex vivo and in vivo evaluation.

The objective of this study was to prepare a transdermal delivery system (TDS) for zidovudine (AZT) with a combination of menthol and oleic acid as penetration enhancers incorporated in hydroxypropyl methylcellulose, and to evaluate ex vivo as well as in vivo permeation across rat skin. It was found that AZT in gel formulation was stable in both refrigerated as well as accelerated stability conditions for 3 months and further, the gel did not significantly retard the permeability of AZT across the skin in comparison with solution formulation. Ex vivo steady state flux of AZT across rat skin from gel was 2.26 mg cm(-2) h(-1), which is sufficient to achieve therapeutic plasma concentrations. Intravenous pharmacokinetic parameters of AZT in rats were determined and used together with ex vivo flux data to generate theoretical plasma profiles of AZT and compared with plasma concentrations achieved after application of TDS. Further, steady state plasma concentrations of drug following multiple applications of TDS were determined and good correlations between ex vivo and in vivo data were observed. In addition, the combination of penetration enhancers used at 2.5% w/w in this study proved efficient in achieving sufficient enhancement in the transdermal permeability of AZT across rat skin with reduced skin irritation potential when compared with individual penetration enhancers at higher concentrations.

Adjuvants, Pharmaceutic↗

PubMed2004

Solid-state characterization of mefenamic acid.

The purpose of this study was to characterize mefenamic acid (MA) from commercial samples and samples crystallized from different solvents. Various techniques used for characterization included microscopy (hot stage microscopy, scanning electron microscopy), intrinsic dissolution rate, differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy and powder X-ray diffractometry (pXRD). The commercial samples varied in their crystal habit, thermal behavior, and intrinsic dissolution rate. It was found that the commercial samples were polymorphic Form I, which converted to Form II on heating in a DSC pan. Similarly, compression in an intrinsic dissolution rate (IDR) press resulted in the conversion of Form I to Form II. On the other hand, the samples recrystallized from different solvents under varying conditions yielded different crystal habits. Stirring and degree of supersaturation significantly influenced the crystal habit in all the solvents used in the study. Samples crystallized from ethanol and tetrahydrofuran yielded Form I, which behaved similarly to the commercial samples (M1 and M3). Recrystallization from ethyl acetate at a fast cooling rate yielded Form I, which on melting crystallized to Form II. The form I crystallized from ethyl acetate by fast cooling converted partially to form II on storing at ambient conditions. Forms I and II of MA were enantiotropically related. The results demonstrate the variable material characteristics of the commercial samples of MA and the influence of the crystallizing conditions on the formation of the polymorphs.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2004

Effect of lipid bilayer alteration on transdermal delivery of a high-molecular-weight and lipophilic drug: studies with paclitaxel.

Skin forms an excellent barrier against drug permeation, due to the rigid lamellar structure of the stratum corneum (SC) lipids. Poor permeability of drugs can be enhanced through alteration in partition and diffusion coefficients, or concentration gradient of drug with an appropriate choice of solvent system, along with penetration enhancers. The aim of the current investigation was to assess applicability of lipid bilayer alteration by fatty acids and terpenes toward the permeation enhancement of a high-molecular-weight, lipophilic drug, paclitaxel (PCL) through rat skin. From among the fatty acids studied using ethanol/isopropyl myristate (1:1) vehicle, no significant enhancement in flux of PCL was observed (p > 0.05). In the case of cis mono and polyunsaturated fatty acids lag time was found to be similar to control (p > 0.05). This suggests that the permeation of a high-molecular-weight, lipophilic drug may not be enhanced by the alteration of the lipid bilayer, or the main barrier to permeation could lie in lower hydrophilic layers of skin. A significant increase in lag time was observed with trans unsaturated fatty acids unlike the cis isomers, and this was explained on the basis of conformation and preferential partitioning of fatty acids into skin. From among the terpenes, flux of PCL with cineole was significantly different from other studied terpenes and controls, and after treatment with menthol and menthone permeability was found to be reduced. Menthol and menthone cause loosening of the SC lipid bilayer due to breaking of hydrogen bonding between ceramides, resulting in penetration of water into the lipids of the SC lipid bilayer that leads to creation of new aqueous channels and is responsible for increased hydrophilicity of SC. This increased hydrophilicity of the SC bilayer might have resulted in unfavorable conditions for ethanol/isopropyl myristate (1:1) along with PCL to penetrate into skin, therefore permeability was reduced. The findings of this study suggest that the permeation of a high-molecular-weight and lipophilic drug cannot be enhanced through bilayer alteration by penetration enhancers, and alteration in partitioning of drug into skin could be a feasible mode to enhance the permeation of drug.

Administration, Cutaneous↗

PubMed2004

Solid-state characterization of rifampicin samples and its biopharmaceutic relevance.

Polymorphism of rifampicin has been postulated to be responsible for its variable bioavailability from solid oral dosage forms. In this regard, it was believed that form II is the preferred form and the content of amorphous needs to be critically monitored. However, there was no study in literature that determines solubility advantage associated with rifampicin polymorphs and further the desired raw material characteristics for the consistent bioavailability. Hence, this investigation was undertaken with an objective to determine biopharmaceutic relevance of rifampicin physical forms and to propose critical raw material specifications for rifampicin bulk material. For this purpose, solid-state properties of standard form I, form II, amorphous and commercial samples acquired from rifampicin manufacturers were characterized by differential scanning calorimetry (DSC), Fourier transformed infrared spectroscopy (FTIR), hot stage microscopy (HSM), thermogravimetric analysis (TGA), powder X-ray diffraction (p-XRD), solid-state nuclear magnetic resonance (NMR) and molecular modelling. In addition, intrinsic dissolution of standard samples, powder dissolution as well as particle size distribution of all the samples and powder dissolution of various sieve fraction of commercial samples were done in order to study the influence of polymorphism and other factors on rate and extent of dissolution. It was found that rifampicin in commercial bulk samples exist as various combinations of form I, form II and amorphous. As physical forms show comparable intrinsic dissolution rate (IDR) at all the pH values, solubility advantage associated with rifampicin polymorphs is negligible. Nevertheless, powder dissolution of commercial samples was influenced by particle size. In powder dissolution of different sieve fractions of commercial samples, fine particles below 100 microm have shown high rate and extent of dissolution irrespective of polymorphic content, whereas particles above 100 microm exhibited reduced dissolution. In intrinsic dissolution, thermodynamically unstable form II exhibited lower IDR than stable form I. Further, this difference is evident only at pH 2.0 and at all other pH values there was no difference in IDR of these two forms. For this unexpected finding, two hypotheses based on differences in H-bonding of the polymorph have been proposed.

Biological Availability↗

PubMed2004

Influence of electrical parameters in the iontophoretic delivery of a small peptide: in vitro studies using arginine-vasopressin as a model peptide.

The present investigation was carried out to understand the influence of electrical parameters on iontophoretic transport of a small peptide like arginine-vasopressin (AVP). In vitro studies using rat skin were conducted to assess the effect of different current densities (CDs), durations, duty cycles and alternating polarity on vasopressin permeation. HPLC was used for ensuring electrochemical stability of the peptide whereas FT-IR and TGA were used to understand the biophysical changes caused in skin due to passage of current. Application of CD > 0.75 mA/cm(2) was found to compromise skin barrier integrity as well as electrochemical stability. Periodic current did not show any significant difference in permeation compared to continuous current. Alternating polarity was useful in reducing pH shift however, was less efficient compared to continuous direct current. FT-IR and TGA studies showed that skin hydration increased as a function of CD and duration and all the results could be explained on the basis of increased skin hydration.

Administration, Cutaneous↗

PubMed2004

The effect of pretreatment with terpenes on transdermal iontophoretic delivery of arginine vasopressin.

This study investigates the effects of terpenes and iontophoresis on the in vitro permeation of arginine vasopressin (AVP) through rat skin and the biophysical changes induced by the chemical enhancers in the stratum corneum (SC) lipids by FT-IR spectroscopy. Pretreatment with terpenes (e.g. 5% w/v, carvone, pulegone, cineole and menthol in EtOH:W (2:1) system) increased (P < 0.05) the flux of AVP in comparison to control (not pretreated with enhancer) but was not significantly different (P > 0.05) in comparison to iontophoresis. Amongst different terpenes studied maximum enhancement ratio was observed with cineole. In combination, iontophoresis did not further increase (P > 0.05) the permeation of AVP through the enhancer pretreated epidermis in comparison to pretreatment with enhancer or iontophoresis alone. Hence it was concluded that although the combination was effective in flux enhancement compared to control, there was no synergism in action between terpenes and iontophoresis. FT-IR spectroscopic studies revealed that EtOH:W (2:1) system is not effective in lipid extraction. The area under the symmetric and asymmetric stretching peaks at 2850 and 2920 cm(-1) revealed that at the concentration used terpenes did not extract any lipids from the epidermis. The mode of action of terpenes is attributed to the breaking of hydrogen bonds between the ceramide head groups of lipids in the SC leading to greater fluidization of the SC lipids.

Administration, Cutaneous↗