Effect Of Penetration Enhancers Research Articles

Ethosomes and organogels for cutaneous administration of crocin.

The present study describes the production and characterization of phosphatidylcholine based ethosomes and organogels, as percutaneous delivery systems for crocin. Crocin presence did not influence ethosome morphology, while the drug slightly increased ethosome mean diameter. Importantly, the poor chemical stability of crocin has been found to be long controlled by organogel. To investigate the performance of phosphatidylcholine lipid formulations as crocin delivery system, in vivo studies, based on tape stripping and skin reflectance spectrophotometry, were performed. Tape stripping results suggested a rapid initial penetration of crocin exerted by the organogel, probably due to a strong interaction between the peculiar supramolecular aggregation structure of phospholipids in the vehicle and the lipids present in the stratum corneum and a higher maintenance of crocin concentration in the case of ethosomes, possibly because of the formation of a crocin depot in the stratum corneum. Skin reflectance spectrophotometry data indicated that both vehicles promoted the penetration of crocin through the skin, with a more rapid anti-inflammatory effect exploited by ethosomes, attributed to an ethanol pronounced penetration enhancer effect and to the carrier system as a whole.

Enhancement of the topical tolnaftate delivery for the treatment of tinea pedis via provesicular gel systems

Tolnaftate is a thiocarbamate antifungal drug which is therapeutically active against dermatophytes that cause various forms of tinea. Due to the small amount of tolnaftate released from ordinary ointment bases and insufficient penetration through the infected skin layers the need to incorporate the drug in a more suitable pharmaceutical form has evolved. A provesicular system is one such form that can solve these problems. Once in contact with the skin, dilution with moisture occurs and the provesicular system rapidly transforms into a vesicular one. Provesicular systems were prepared according to full-factorial experimental design. Plain provesicular systems were compared with systems containing Phospholipon 80 H and Lipoid S45 as penetration enhancers. Design expert software was used to analyze the effect of formulation variables (type of Span used as well as the presence or the absence of the penetration enhancer and its type) on the dependent variables: percent encapsulation efficiency (EE%), vesicle size and percent in vitro drug released). Three formulations were chosen; a plain provesicular system (PV-2), one containing Phospholipon 80H (PV-6) and another containing Lipoid S45 (PV-10) with the goal to reveal the effect of penetration enhancer on morphology, rheological properties and ex vivo permeation using confocal laser scanning microscopy (CLSM). Analysis of CLSM results showed that the penetration enhancing effect for the tested formulations followed the order PV-10 > PV-6 > PV-2. Promising clinically active treatment for tinea patients could be expected as shown by the in vivo permeation results for the provesicular systems as suggested by the CLSM results.

Polymeric nanocapsules: a potential new therapy for corneal wound healing

Corneal injuries are one of the most frequently observed ocular diseases, leading to permanent damage and impaired vision if they are not treated properly. In this sense, adequate wound healing after injury is critical for keeping the integrity and structure of the cornea. The goal of this work was to assess the potential of polymeric nanocapsules, either unloaded or loaded with cyclosporine A or vitamin A, alone or in combination with mitomycin C, for the treatment of corneal injuries induced by photorefractive keratectomy surgery. The biopolymers selected for the formation of the nanocapsules were polyarginine and protamine, which are known for their penetration enhancement effect. The results showed that, following topical instillation to a mouse model of corneal injury, all the nanocapsule formulations, either unloaded or loaded with cyclosporine A or vitamin A, were able to stimulate corneal wound healing. In addition, the healing rate observed for the combination of unloaded protamine nanocapsules with mitomycin C was comparable to the one observed for the positive control Cacicol®, a biopolymer known as a corneal wound healing enhancer. Regarding the corneal opacity, the initial grade of corneal haze (>3) induced by the photorefractive keratectomy was more rapidly reduced in the case of the positive control, Cacicol®, than in corneas treated with the nanocapsules. In conclusion, this work shows that drug-free arginine-rich (polyarginine, protamine) nanocapsules exhibit a positive behavior with regard to their potential use for corneal wound healing.

Effect of pH and penetration enhancers on cysteamine stability and trans-corneal transport

Ocular cystinosis is a rare metabolic disorder characterized by the presence of insoluble cystine crystals inside the corneal stroma, with consequent photophobia, keratopathies and frequent corneal erosions. The current therapy consists in the lifetime ophthalmic administration of cysteamine, drug characterized by extremely high hydrophilicity, low molecular weight (77g/mol), and easy oxidization to disulfide. Ocular delivery of cysteamine is very challenging, for its poor permeability and stability in solution. The purpose of the present paper was to study the impact of formulation pH and composition on (1) the trans-corneal delivery and (2) the stability in solution of cysteamine, with particular focus on the use of alpha-cyclodextrin (α-CD), benzalkonium chloride (BAC) and disodium edetate (EDTA). Permeation experiments were performed ex vivo through freshly excised porcine cornea; stability was evaluated for six months at −20°, +4° and +25°C; irritation potential was evaluated using HET-CAM assay. The results showed that cysteamine trans-corneal diffusion is strictly dependent on both pH (7.4 preferred to 4.2) and buffering capacity, that negatively impact on the permeation; EDTA did not enhance the trans-corneal diffusion of cysteamine neither at pH 7.4 nor at pH 4.2, while benzalkonium chloride (BAC), antimicrobial agent present within commercial eye-drops, significantly enhanced it. Notably, α-CD was able to promote the trans-corneal diffusion of cysteamine and, at a 5.5%, a 4-fold higher penetration compared to the BAC-containing formulation was obtained. EDTA and acidic pH demonstrated to be essential for cysteamine stability. The formulation obtained by combining α-CD and EDTA was characterized by significant permeation, good stability profile, and no irritation potential, even if the tolerability should be further confirmed by in vivo test.

Association between chemical composition of essential oil with penetration enhancement effect and drug properties of traditional Chinese medicine

The results of previous studies showed potential correlations between the penetration enhancement effect of essential oils and the drug properties of traditional Chinese medicine based on the data mining method. As chemical composition is the material basis of drug properties of traditional Chinese medicine, this article further analyzed the correlation between the chemical composition of essential oils and the drug properties. Firstly, essential oils were extracted by steam distillation, and then physicochemical parameters of essential oils, such as relative density and refractive index, were measured. The chemical components of 20 essential oils were analyzed by GC-MS, and divided into 12 categories according to skeleton features and functional groups. Finally, Logistic regression analysis was applied to reveal the correlations. The results proved that five flavors, four tastes and channel tropisms showed the correlation with chemical composition of essential oils (P<0.05). In conclusion, there were obvious correlations and regularity between the drug properties of traditional Chinese medicine and the chemical composition of essential oils.

Transdermal permeation of Zanthoxylum bungeanum essential oil on TCM components with different lipophilicity

ObjectiveTo investigate the percutaneous penetration enhancement effect of essential oil from Zanthoxylum bungeanum Maxim. (Z. bungeanum oil) on active components in externally-applied traditional Chinese medicines. MethodsFive model drugs, geniposide, puerarin, ferulic acid, tetramethylpyrazine, and osthole, were chosen based on their lipophilicity and tested using in vitro transdermal permeation studies consisting of Franz diffusion cells and full thickness rat abdominal skin. Scanning electron microscopy was employed to observe the morphological changes of rat skin tissue after treatment with Z. bungeanum oil. The molecular interactions between the oil and the polar head groups in stratum corneum (SC) lipids were monitored using molecular dynamic simulation, and the SC/vehicle partition coefficients and saturation solubilities of the selected model drugs treated with and without the oil were also determined to ascertain its mechanisms of action. ResultsAs oil concentration increased, the log ERflow trended toward a negative linear relationship with the lipophilicity of drugs. After treatment with Z. bungeanum oil, a mild lifting up and wrinkle on the SC surface were observed, and appeared to become more pronounced as oil concentration increased. There was no significant difference between the control and the Z. bungeanum oil at different concentrations in terms of saturation solubility of GP, while saturation solubilities of the 4 other drugs gradually increased as oil concentration increased. The oxygen-containing constituents in Z. bungeanum oil, such as terpinen-4-ol and 1,8-cineole, which accounted for 57.95% of total oil, could form stable hydrogen bonds with the polar head group of ceramide 3. ConclusionZ. bungeanum oil facilitated transdermal permeation of drugs with different lipophilicity, including the extremely hydrophilic and lipophilic drugs, whereas it exhibited greater enhancement activity for strongly hydrophilic drugs. The mechanisms of transdermal permeation enhancement by the oil could be explained with SC/vehicle partition coefficient, saturation solubility, and the interactions with SC lipids.

Development of gellan gum containing formulations for transdermal drug delivery: Component evaluation and controlled drug release using temperature responsive nanogels

Enhancing skin permeation is important for development of new transdermal drug delivery formulations. This is particularly relevant for non-steroidal anti-inflammatory drugs (NSAIDs). To address this, semisolid gel and solid hydrogel film formulations containing gellan gum as a gelling agent were developed and the effects of penetration enhancers (dimethyl sulfoxide, isopropyl alcohol and propylene glycol) on transport of the NSAID diclofenac sodium was quantified. A transwell diffusion system was used to accelerate formulation development. After 4h, diclofenac flux from a superior formulation of the semisolid gel or the solid hydrogel film was 130±11μg/cm2h and 108±7μg/cm2h, respectively, and significantly greater than that measured for a currently available diclofenac sodium topical gel (30±4μg/cm2h, p<0.05) or solution formulation (44±6μg/cm2h, p<0.05) under identical conditions. Over 24h diclofenac transport from the solid hydrogel film was greater than that measured for any new or commercial diclofenac formulation. Entrapment of temperature-responsive nanogels within the solid hydrogel film provides temperature-activated prolonged release of diclofenac. Diclofenac transport was minimal at 22°C, when diclofenac is entrapped within temperature-responsive nanogels incorporated into the solid hydrogel film, but increased 6-fold when the temperature was increased to skin surface temperature of 32°C. These results demonstrate the feasibility of the semisolid gel and solid hydrogel film formulations that can include thermo-responsive nanogels for development of transdermal drug formulations with adjustable drug transport kinetics.

The effect of urea and taurine as hydrophilic penetration enhancers on stratum corneum lipid models

To optimize transdermal application of drugs, the barrier function of the skin, especially the stratum corneum (SC), needs to be reduced reversibly. For this purpose, penetration enhancers like urea or taurine are applied. Until now, it is unclear if this penetration enhancement is caused by an interaction with the SC lipid matrix or related to effects within the corneocytes. Therefore, the effects of both hydrophilic enhancers on SC models with different dimensionality, ranging from monolayers to multilayers, have been investigated in this study. Many sophisticated methods were applied to ascertain the mode of action of both substances on a molecular scale. The experiments reveal that there is no specific interaction when 10% urea or 5% taurine solutions are added to the SC model systems. No additional water uptake in the head group region and no decrease of the lipid chain packing density have been observed. Consequently, we suppose that the penetration enhancing effect of both substances might be based on the introduction of large amounts of water into the corneocytes, caused by the enormous water binding capacity of urea and a resulting osmotic pressure in case of taurine.

Preparation of a New Oligolamellar Stratum Corneum Lipid Model.

In this study, we present a preparation method for a new stratum corneum (SC) model system, which is closer to natural SC than the commonly used multilayer models. The complex setup of the native SC lipid matrix was mimicked by a ternary lipid mixture of ceramide [AP], cholesterol, and stearic acid. A spin coating procedure was applied to realize oligo-layered samples. The influence of lipid concentration, rotation speed, polyethylenimine, methanol content, cholesterol fraction, and annealing on the molecular arrangement of the new SC model was investigated by X-ray reflectivity measurements. The new oligo-SC model is closer to native SC in the total number of lipid membranes found between corneocytes. The reduction in thickness provides the opportunity to study the effects of drugs and/or hydrophilic penetration enhancers on the structure of SC in full detail by X-ray or neutron reflectivity. In addition, the oligo-lamellar systems allows one to infer not only the lamellar spacing, but also the total thickness of the oligo-SC model and changes thereof can be monitored. This improvement is most helpful for the understanding of transdermal drug administration on the nanoscale. The results are compared to the commonly used multilamellar lipid model systems and advantages and disadvantages of both models are discussed.

Chemical penetration enhancers in stratum corneum — Relation between molecular effects and barrier function

Skin is attractive for drug therapy because it offers an easily accessible route without first-pass metabolism. Transdermal drug delivery is also associated with high patient compliance and through the site of application, the drug delivery can be locally directed. However, to succeed with transdermal drug delivery it is often required to overcome the low permeability of the upper layer of the skin, the stratum corneum (SC). One common strategy is to employ so-called penetration enhancers that supposedly act to increase the drug passage across SC. Still, there is a lack of understanding of the molecular effects of so-called penetration enhancers on the skin barrier membrane, the SC. In this study, we provide a molecular characterization of how different classes of compounds, suggested as penetration enhancers, influence lipid and protein components in SC. The compounds investigated include monoterpenes, fatty acids, osmolytes, surfactant, and Azone. We employ natural abundance 13C polarization transfer solid-state nuclear magnetic resonance (NMR) on intact porcine SC. With this method it is possible to detect small changes in the mobility of the minor fluid lipid and protein SC components, and simultaneously obtain information on the major fraction of solid SC components. The balance between fluid and solid components in the SC is essential to determine macroscopic material properties of the SC, including barrier and mechanical properties. We study SC at different hydration levels corresponding to SC in ambient air and under occlusion. The NMR studies are complemented with diffusion cell experiments that provide quantitative data on skin permeability when treated with different compounds. By correlating the effects on SC molecular components and SC barrier function, we aim at deepened understanding of diffusional transport in SC, and how this can be controlled, which can be utilized for optimal design of transdermal drug delivery formulations.

Confocal Raman microscopy and multivariate statistical analysis for determination of different penetration abilities of caffeine and propylene glycol applied simultaneously in a mixture on porcine skin ex vivo

Propylene glycol is one of the known substances added in cosmetic formulations as a penetration enhancer. Recently, nanocrystals have been employed also to increase the skin penetration of active components. Caffeine is a component with many applications and its penetration into the epidermis is controversially discussed in the literature. In the present study, the penetration ability of two components – caffeine nanocrystals and propylene glycol, applied topically on porcine ear skin in the form of a gel, was investigated ex vivo using two confocal Raman microscopes operated at different excitation wavelengths (785nm and 633nm).Several depth profiles were acquired in the fingerprint region and different spectral ranges, i.e., 526–600cm−1 and 810–880cm−1 were chosen for independent analysis of caffeine and propylene glycol penetration into the skin, respectively. Multivariate statistical methods such as principal component analysis (PCA) and linear discriminant analysis (LDA) combined with Student’s t-test were employed to calculate the maximum penetration depths of each substance (caffeine and propylene glycol). The results show that propylene glycol penetrates significantly deeper than caffeine (20.7–22.0μm versus 12.3–13.0μm) without any penetration enhancement effect on caffeine. The results confirm that different substances, even if applied onto the skin as a mixture, can penetrate differently.The penetration depths of caffeine and propylene glycol obtained using two different confocal Raman microscopes are comparable showing that both types of microscopes are well suited for such investigations and that multivariate statistical PCA–LDA methods combined with Student’s t-test are very useful for analyzing the penetration of different substances into the skin.

Effects of different penetration enhancers on pharmacokinetics of active components in Xiangfu Siwu transdermal patches

To study the effect of different penetration enhancers on the pharmacokinetic characters of six active components in Xiangfu Siwu transdermal patch (XBW) and optimize the best penetration enhancers. During the experiment, the patches containing different penetration enhancers were stuck on the rat's skin, and then the blood samples were acquired at different time points. Six active components in plasma were determined by UPLC-MS/MS. The main pharmacokinetic parameters were calculated with DAS software package. The total factor scores (F) of the plasma concentrations of six components at every time point in different groups were calculated using principle component analysis, and the areas under F versus time curves (AUCF-t) were employed to be the indexes for selecting penetration enhancers. The results demonstrated that compared with the control group, the AUCF-t from other groups increased prominently and furthermore, 5% menthol manifested the best effect. In this research, 5% menthol could remarkably promote the percutaneous penetration effect of the six active compounds in XBW, and it could provide a scientific basis for the preparation research of XBW.

Essential Fatty Acids as Transdermal Penetration Enhancers

The aim of this study was to investigate the effect of different penetration enhancers, containing essential fatty acids (EFAs), on the transdermal delivery of flurbiprofen. Evening primrose oil (EPO), vitamin F, and Pheroid™ technology all contain fatty acids and were compared using a cream-based formulation. This selection was to ascertain whether EFAs solely, or EFAs in a Pheroid™ delivery system, would have a significant increase in the transdermal delivery of a compound. Membrane release studies were performed, and the results indicated the following rank order for flurbiprofen release from the different formulations: vitamin F >> control > EPO >> Pheroid™. Topical skin delivery results indicated that flurbiprofen was present in the stratum corneum–epidermis and the epidermis–dermis. The average percentage flurbiprofen diffused to the receptor phase (representing human blood) indicated that the EPO formulation showed the highest average percentage diffused. The Pheroid™ formulation delivered the lowest concentration with a statistical significant difference (p < 0.05) compared with the control formulation (containing 1% flurbiprofen and no penetration enhancers). The control formulation presented the highest average flux, with the EPO formulation following the closest. It could, thus, be concluded that EPO is the most favorable chemical penetration enhancer when used in this formulation.

Double emulsions based on silicone-fluorocarbon-water and their skin penetration

Double emulsions have significant potential in pharmacy and cosmetics due to the feasibility of combining incompatible substances in one product and the protection of sensitive compounds by incorporating them into their innermost phase. However, a major drawback of double emulsions is their thermodynamic instability and their strong tendency to coalesce. In the present study, the physicochemical stability, the skin permeation and the skin penetration potential of modified semi-solid double emulsions was investigated. The double emulsions were prepared of the cosmetically applied perfluoropolyethers Fomblin® HC/04 or Fomblin® HC-OH, silicone, carbomer and water. Measurement of the droplet size and examination of the microscopic images confirmed their physicochemical stability over the observation period of eight weeks. Franz-type diffusion cell experiments revealed no increase in curcumin permeation due to the employed perfluoropolyethers compared to the respective control formulations. The formulations used as control were O/W macroemulsions with or without a Polysorbate 80/Sorbitane monooleate 80 surfactant combination. Likewise, tape stripping studies showed no penetration enhancing effect of the employed perfluoropolyethers which is desirable as both perfluoropolyethers are commonly applied components in human personal-care products.

Association between penetration enhancement effect of essential oils and drug properties of traditional Chinese medicines by data mining method

To study the association between penetration enhancement effect of essential oils and drug properties of traditional Chinese medicines. Through literature research, 34 kinds of essential oils with the penetration enhancement effect were collected. The methods of frequency analysis and variable crosstab were used for intuitive analysis and association analysis. The association between penetration enhancement effect of essential oils and drug properties (four natures, five flavors, channel tropism) were analyzed by a general linear model. According to the findings, the essential oils with penetration enhancement effect were all sourced from acrid traditional Chinese medicines, because their positive drug nature contributed to the enhancement of the penetration effect of essential oil; five flavors had little effect on penetration enhancement (P = 0.6982), but four natures and channel tropism showed significant effects (P = 0.011, 0.077). In conclusion, there were obvious association and regularity between penetration enhancement effect of essential oils and drug properties of traditional Chinese medicine.

Effect of chemical penetration enhancer on transdermal iontophoretic delivery of diclofenac sodium under constant voltage

The study aimed to enhance the transdermal permeation of diclofenac sodium using combined strategy of constant voltage iontophoresis (CVI) and chemical penetration enhancers (CPE). Four hydrogels of diclofenac sodium were formulated with the key CPE and hydroxyethyl cellulose (HEC) as a viscosity imparting agent. In vitro permeation studies of the hydrogels indicated CVI significantly increased (ANOVA, P < 0.05) the steady state flux of diclofenac sodium through the porcine skin in the order geraniol (F1) > l-menthol (F2) > thymol (F3) > SLS-urea (F4) compared to the Fc (Passive control) under the applied voltage. F1 was identified as the lead formulation as an overall increase in steady state flux of 5.157 fold compared to Fc was observed at 1.5V. Pharmacokinetic studies in rats indicated that CVI at 1.5V following application of the lead formulation increased the Cmax and AUC0-8h by ∼3.5 folds compared to passive treatment. The higher systemic levels of diclofenac are likely to enhance the drug concentration in synovial fluid which is the site of action in most musculoskeletal disorders. The results of the study indicate that CVI can effectively deliver therapeutic amounts of diclofenac sodium transdermally to relieve chronic deep-seated muscular pain in several rheumatic disorders.

Influence of sonophoresis and chemical penetration enhancers on percutaneous transport of penbutolol sulfate

The effect of ultrasound and chemical penetration enhancers on transcutaneous flux of penbutolol sulfate across split-thickness porcine skin was investigated. Penbutolol sulfate is a potent, noncardioselective beta-blocker, which is used for the management of hypertension. The drug is one of the most lipid soluble of the β-adrenoceptor antagonists used clinically. It has an n-octanol/pH 7.4 buffer partition coefficient of 179 compared to a value of 22 for propranolol. The amount of penbutolol sulfate transported across the skin is low. In this project, we studied the effect of sonophoresis and chemical penetration enhancers on transdermal delivery of penbutolol sulfate. Low-frequency sonophoresis at a frequency of 20 kHz increased transcutaneous flux of penbutolol sulfate by 3.5-fold (27.37 ± μg cm−2 h−1) compared to passive delivery (7.82 ± 1.72 μg cm−2 h−1). We also investigated the effect of 50% ethanol, 1% limonene and 2% isopropyl myristate (IPM) on transcutaneous permeation of penbutolol sulfate. IPM, ethanol and limonene at the concentration of 1%, 50% and 2%, respectively, increased the steady-state flux values of penbutolol sulfate 2.2- (17.07 ± 3.24 μg cm−2 h−1), 2.6 - (19.40 ± 6.40 μg cm−2 h−1) and 3.4-times (26.38 ± 5.01 μg cm−2 h−1) compared to passive delivery (7.76 ± 2.9 μg cm−2 h−1). The results demonstrate that although there were slight increases in flux values, ultrasound, ethanol, limonene and IPM did not significantly enhance the transdermal delivery of penbutolol sulfate. Future studies will examine ways of optimizing sonophoretic and chemical enhancer parameters to achieve flux enhancement.

New Approach of Sucrose Myristate as a Promising Penetration Enhancer in Dermal Preparations

AbstractThe aim of this work was to compare the penetration enhancer effect of newly developed sucrose myristate with the generally used sucrose laurate. Hydrogel formulations containing sucrose esters (SEs) were prepared and the model drug was Ibuprofen (IBU), which has oral side effects, so applying it in a transdermal system could be useful. We evaluated the effect of SE hydrogel formulations on the skin by the noninvasive in vivo test and examined their concentration dependent influence on the penetration of IBU through a synthetic membrane (in vitro) by the Franz cell method. The results indicated that sucrose myristate incorporated into hydrogel moistures the skin well and lastingly and showed a better drug penetration enhancing effect at a much lower concentration compared to sucrose laurate. Our results revealed that sucrose myristate could be a promising and effective penetration enhancer in the pharmaceutical field.

Transdermal delivery of Diltiazem HCl from matrix film: Effect of penetration enhancers and study of antihypertensive activity in rabbit model

The present investigation focused on the development of Diltiazem HCl (DTH) matrix film and its characterization by in-vitro, ex-vivo and in-vivo methods. Films were prepared by solvent casting method by taking different ratios of hydroxypropyl methylcellulose K4M (HPMC K4M) and Eudragit RS100. Various parameters of the films were analyzed such as mechanical property using tensile tester, interaction study by Fourier transform infrared spectroscopy (FTIR) and Thermogravimetric analysis (TGA), in-vitro drug release through cellulose acetate membrane, ex-vivo permeation study using abdominal skin of rat employing Franz diffusion cell, and in-vivo antihypertensive activity using rabbit model. The FTIR studies confirmed the absence of interaction between DTH and selected polymers. Thermal analysis showed the shifting of endothermic peak of DTH in film, indicating the dispersion of DTH in molecular form throughout the film. Incorporation of 1,8-cineole showed highest flux (89.7μg/cm2/h) of DTH compared to other penetration enhancers such as capsaicin, dimethyl sulfoxide (DMSO), and N-methyl pyrrolidone (NMP). Photomicrographs of histology study on optimized formulation (DF9) illustrated disruption of stratum corneum (SC) supporting the ex-vivo results. The in-vivo antihypertensive activity results demonstrated that formulation DF9 was effective in reducing arterial blood pressure in normotensive rabbits. SEM analysis of films kept for stability study (40±2°C/75%±5%RH for 3months) revealed the formation of drug crystals which may be due to higher temperature. The findings of the study provide a better alternative dosage form of DTH for the effective treatment of hypertension with enhanced patient compliance.

Penetration Enhancement Effect of Turpentine Oil on Transdermal Film of Ketorolac

Purpose: To prepare transdermal films of ketorolac tromethamine (KT) and study the effect of turpentine oil as a penetration enhancer for the drug. Methods: Transdermal films of KT were prepared with Carbopol-934 and ethyl cellulose, with turpentine oil as the penetration enhancer, using solvent evaporation method. The films were characterized for physicochemical properties, ex vivo permeation, as well as in vivo anti-inflammatory and analgesic activities in Wistar rats. Results: The transdermal films were uniform in weight and thickness, flat, with high drug content (93.9 to 98.5 %) and of high folding endurance (134.0 to 180.0). Drug permeation through excised rat abdominal skin was prolonged, with the total drug release ranging from 58.88 to 88.98 % in 24 h. The films containing penetration enhancer showed higher drug permeation than the one without the enhancer; furthermore, drug permeation increased with increase in the concentration of the enhancer. The films were non-irritant to the skin. The transdermal films prepared with permeation enhancers showed greater anti-inflammatory activity (87.55 ± 2.50 and 83.24 ± 2.29 % inhibition of rat paw edema at the end of 12 h for formulations F2 and F3, respectively, compared to that of the formulation without enhancer with 69.99 %) as well as greater analgesic activity (quicker onset of analgesia in 1.5 h with longer duration of 10 to 12 h). Conclusion: Transdermal films of ketorolac have a potential for use in the treatment of pain andinflammation. Incorporation of turpentine oil in the films enhances not only drug flux but also analgesic and anti-inflammatory activities in rats.