The single-pass perfused rabbit ear as a model for studying percutaneous absorption of clonazepam. I. General characteristics.

A single-pass perfused rabbit ear was employed as the model for studying percutaneous absorption of clonazepam in an open perfusion system. Clonazepam at 1.5% concentration (w/w) was suspended in a gel containing 1% (w/w) neutralized Carbopol 934 vehicled by a 50% water solution of propylene glycol and applied to the skin, in a thermostatically controlled chamber, after 10 min pretreatment with a lauryl alcohol enhancer. At 32 degrees C, the amount of clonazepam which diffused into the effluent after a 3 h lag phase was constant for 3 h and the flux averaged 0.486 mcg/h/cm2, whereas at 25 degrees C, the flux averaged 0.424 mcg/h/cm2. The amount of drug diffusing into the effluent was a function of the contact surface area and was independent of the rate of perfusion up to values of 1 ml/min. The apparent diffusion coefficient, Ds, and the partition coefficient, KM, were 2.75/10(6)/cm/h and 5.21, respectively.     

Modelling transdermal drug delivery using microneedles: effect of geometry on drug transport behaviour

Transdermal drug delivery using microneedles (MNs) depends on the rate of drug transport through the viable epidermis. Therefore, minimising the distance between the drug-loaded surface and the microcirculation in the dermis where the drug is absorbed into the body is significant in improving drug delivery efficiency. A quantifiable relationship between MN design parameters and skin diffusion properties is therefore desirable, which is what this study aims to achieve. A framework is presented to quantitatively determine the effects of design parameters on drug diffusion through skin, where the effects of compressive strain on skin due to insertion of MN are considered. The model is then used to analyse scenarios of practical importance. For all scenarios analysed, predicted steady-state flux was found to be lower when effect of MN strain on diffusion coefficient was accounted for. For example, simulations results indicated increasing tip radius from 5 to 20 μm and flux increased from 6.56 × 10(-6) to 7.02 × 10(-6) mol/(m(2) s) for constant diffusion coefficient. However, if the effect of strain on diffusion coefficient is considered, the calculated flux increases from 5.30 × 10(-6) to a peak value of 5.32 × 10(-6) mol/(m(2) s) (at 10 μm) and decreases to 5.29 × 10(-6) mol/(m(2) s). This paper contributes by reporting a framework to relate MN geometry to permeability with inclusion of the possible effects the MN design may pose on the diffusion coefficient.     

Vehicle effects on in vitro release of tiaprofenic acid from different topical formulations

The aim of the present study was to investigate the in vitro release properties of tiaprofenic acid (TA) from different topical vehicles. Carbopol 940 gel, chitosan gel, two types of emulsion-based ointment formulations (o/w and w/o) and hydrophilic petrolatum USP were prepared with 2% drug content. Drug release from all vehicles through a standard cellophane membrane was evaluated by using Franz-type diffusion cells. In vitro release study results showed that the diffusion coefficients of the drug from vehicles rank according to the following order: Carbopol 940 gel (D = 3.11 x 10(-7) +/- 0.54 cm(2)/s) > chitosan gel (D = 0.27 x 10(-7) +/- 0.08 cm(2)/s) > emulsion-based ointment (o/w) (D = 0.18 x 10(-7) +/- 0.05 cm(2)/s) > emulsion-based ointment (w/o) (D = 0.13 x 10(-7) +/- 0.02 cm(2)/s) > hydrophilic petrolatum USP (D = 0.02 x 10(-7) +/- 0.01 cm(2)/s). Carbopol 940 gel base showed significantly higher drug release than other vehicles (P < 0.001). These results indicated that Carbopol 940 gel base is a good candidate for the topical delivery of TA, giving significantly higher drug release than the other vehicles.     

Rapid human skin permeation and topical anaesthetic activity of a new amethocaine microemulsion

We developed a fast-acting, topical, 4% (w/w) amethocaine microemulsion and tested its in vitro permeation in isolated human skin. Comparison with a commercial amethocaine gel (Ametop((R)) ) was performed using Franz diffusion cells. Permeability coefficient (k(p)), flux (J) and percentage permeation after 10 h of microemulsion application were, in all cases, 1.5 times higher than those of the gel. The values obtained for the P(1) parameter [1], 1.06.10(-2) cm (microemulsion) and 0.724.10(-2) cm (gel) indicate that the microemulsion excipients favour amethocaine deposition in the skin, increasing the permeability coefficient, amount of drug retained in the skin, and the flux achieved. Analgesic activity was also examined in rats made hyperalgesic or allodynic after carrageenan-induced inflammation. The rats were distributed into four groups (n = 5-9 per group), each group receiving topically either amethocaine microemulsion, amethocaine gel (Ametop), amethocaine subcutaneous infiltration or nothing (controls). In edematous paws, anti-hyperalgesic activity appeared at 4.2 and 13.8 min after application of amethocaine microemulsion and gel, respectively. These effects are lower than after 0.5% w/w amethocaine infiltration. Amethocaine microemulsion was the only topical formulation with an anti-allodynic effect, although this effect was less than with amethocaine infiltration. These results suggest that microemulsion could be a valuable formula for improving amethocaine permeation and thus bringing rapid pain relief.     

Transdermal application of bupivacaine-loaded poly(acrylamide(A)-co-monomethyl itaconate) hydrogels

Bupivacaine, an amide local anaesthetic agent of long-acting and intense anaesthesia, was incorporated into poly(acrylamide(A)-co-monomethyl itaconate (MMI)) hydrogels. The swelling behaviour of two gel compositions, without drug, 75A/25MMI and 60A/40MMI, through rabbit ear skin, mounted on a modified Franz diffusion cell, was studied. Both gel compositions reach the equilibrium swelling degree (88.9+/-0.7 wt.% for 75A/25MMI and 92.5+/-0.1 wt.% for 60A/40MMI). The swelling kinetics was in accordance with the second Fick's Law; diffusion coefficients indicate faster swelling for gels with lower amount of monomethyl itaconic acid. The skin flux of bupivacaine solution through rabbit ear skin was 105+/-24 microg/cm(2)/h, the effective permeability coefficient was 26 x 10(-3)+/-9 x 10(-3)cm/h, and 77+/-15% of bupivacaine was permeated. Bupivacaine-loaded gels allow the drug was permeated through the skin. 47+/-4% and 36+/-3% of the drug amount included in 75A/25MMI and 60A/40MMI hydrogels, respectively, was permeated. The skin flux of the drug was between 90+/-5 and 16+/-7 microg/cm(2)/h depending on the amount of bupivacaine included in the gel and the gel composition. Skin flux increases with the drug load of the gels. Furthermore, as more MMI in the gel slower skin flux of the drug due to bupivacaine-gel interactions.     

胶原蛋白凝胶的制备及其中药物体外扩散性考察

目的:提取鱼鳞胶原蛋白,制成凝胶并考察其中药物的体外扩散性。方法:鱼鳞经胃蛋白酶提取、盐析、纯化、冷冻干燥得到胶原蛋白。以水杨酸为模型药物,加入柠檬酸溶液、甘油和乙醇混合液制备胶原蛋白凝胶,并采用琼脂扩散法以扩散系数k为指标评价其体外扩散性,同时与水杨酸水溶性和油脂性软膏进行比较。结果:所得胶原蛋白含量为91.04%;所制水杨酸胶原蛋白凝胶及水溶性和油脂性软膏扩散系数k值分别为68.11、58.04、17.67mm2·h-1。结论:所制凝胶中药物体外扩散速率较快,胶原蛋白可作为载体用于需较快释放药物的外用制剂。     

SDS-aided immobilization and controlled release of camptothecin from agarose hydrogel.

Camptothecin (CPT), known to be an effective anticancer drug, has a limited therapeutic utility because of its poor water solubility. In this work, an approach has been made to overcome the limitation. CPT was first incorporated into the micelles formed from an ionic surfactant, sodium dodecyl sulfate (SDS) and the micellar drug aqueous solution was then used in preparation of the agarose hydrogel. It has been found that the presence of SDS greatly increased the solubility of CPT in water. For example, in 1 ml of 1.0 wt.% SDS water solution, 0.11 mg CPT could be solubilized (0.318 mM), which was 83 times the solubility in pure water. It was the hydrophobic cores of the SDS micelles that were able to accept the lipophilic drug to form stable drug-immobilized micelles. The formulation of a hydrogel using the drug-immobilized micelles has allowed us to obtain a unique and novel drug release system where the drug molecules are encapsulated by the micelles and the drug-containing micelles are dispersed in the gel network. The release of CPT from the so deliberately fabricated agarose hydrogel system has been studied as a function of surfactant concentration at 37 degrees C. The diffusion coefficients of CPT obtained by fitting to Fick's law ranged from 2.12 to 7.36 x 10(-7)cm(2)s(-1). The results showed that SDS prolonged the drug release by reducing the diffusion coefficient of CPT in the gel.     

The release dynamics of model drugs from the psyllium and N-hydroxymethylacrylamide based hydrogels

In order to utilize the psyllium husk, a medicinally important natural polysaccharide, for developing the novel hydrogels for the controlled drug delivery device, we have prepared psyllium and N-hydroxymethylacrylamide based polymeric networks by using N,N'-methylenebisacrylamide (N,N'-MBAAm) as crosslinker. The polymeric networks thus formed were characterized with scanning electron micrography (SEM), FTIR and thermogravimetric analysis (TGA) techniques to study various structural aspects of the networks and also with the swelling response of the polymeric networks as a function of time, temperature, pH and [NaCl]. Equilibrium swelling has been observed to depend on both structural aspects of the polymers and environmental factors. Maximum P(s) 748.3 was observed at 13.0 x 10(-3)mol/L of [N,N'-MBAAm] in 0.5M NaOH solution. The release dynamics of model drugs (salicylic acid and tetracycline hydrochloride) from hydrogels has also been discussed, for the evaluation of the release mechanism and diffusion coefficients. The effect of pH on the release pattern of tetracycline has been studied by varying the pH of the release medium. In release medium of pH 7.4 buffer the release pattern of tetracycline drastically changes to the extent that mechanism of drug diffusion shifted from non-Fickian diffusion to Fickian diffusion. It has been observed that diffusion exponent "n" have 0.71, 0.67 and 0.52 values and gel characteristic constant 'k' have 1.552 x 10(-2), 2.291 x 10(-2) and 5.309 x 10(-2) values in distilled water, pH 2.2 buffer and pH 7.4 buffer, respectively, for tetracycline release. In solution of pH 7.4 buffer, the rate of polymer chain relaxation was more as compare to the rate of drug diffusion from these hydrogels and it follows Fick's law of diffusion. The value of the initial diffusion coefficient for the release of tetracycline hydrochloride was higher than the value of late time diffusion coefficient in each release medium indicating that in the start, the diffusion of drug from the polymeric matrix was fast as compare to the latter stages.     

Meloxicam β-cyclodextrin transdermal gel: physicochemical characterization and in vitro dissolution and diffusion studies

The aim of the study was to develop a Meloxicam (ME) transdermal gel formulations based on complexation with β-cyclodextrin. ME β-Cyclodextrin gel formulations were prepared using four different gel bases with different concentrations and different permeation enhancers. The developed formulations were examined for their in vitro characteristics and their diffusion through a mouse skin. The gel formulations were prepared successfully. Physicochemical characterization of ME β-CD complex in solution state by phase solubility revealed 1:1 M complexation of ME with β-Cyclodextrin. ME release profiles from the inclusion complex were superior over ME alone. Hydroxypropyl methyl cellulose 15% w/w gel base was proven to be a suitable base for ME inclusion complex formulation as it provides a high drug release than other studied bases. ME β-CD complex gel formulations containing oleic acid (1% w/w) or (5% w/w) cineol used as permeation enhancers in (15% w/w) HPMC gel base were proven to provide a higher diffusion rate of the drug through the mouse skin. This is very promising in providing analgesic activity of meloxicam via topical route of administration.     

A novel impinging aerosols method for production of propranolol hydrochloride-loaded alginate gel microspheres for oral delivery

Propranolol hydrochloride was directly encapsulated in alginate gel microspheres (40-50?μm in diameter) using a novel method involving impinging aerosols of CaCl(2) cross-linking solution and sodium alginate solution containing the drug. Microspheres formulated using 0.1?M CaCl(2) exhibited the highest drug loading (14%, w/w of dry microspheres) with 66.5% encapsulation efficiency. Less than 4% and 35% propranolol release occurred from hydrated and dried microspheres, respectively, in 2?h in simulated gastric fluid (SGF). The majority of the drug load (90%) was released in 5 and 7?h from hydrated and dried microspheres, respectively, in simulated intestinal fluid (SIF). Prior incubation of hydrated microspheres (cross-linked using 0.5?M CaCl(2)) in SGF prolonged the time of release in SIF to 10?h, which has implications for the design of protocols and correlation with in?vivo release behaviour. Restricted propranolol release in SGF and complete extraction in SIF demonstrate the potential of alginate gel microspheres for oral delivery of pharmaceuticals.     

Effect of ethanol on the true diffusion coefficient of diclofenac and its sodium salt in silicone membrane

The effect of ethanol on the diffusion coefficient of free diclofenac (DH) as a hydrophobic drug in a silicone membrane was studied and the value was compared with that of sodium diclofenac (DNa) as a hydrophilic material. The silicone membrane permeation of DH was described as a lipid pathway up to 60% w/w ethanol. The change in the partition coefficient of DH between the silicone membrane and ethanol-aqueous solution as a function of ethanol concentration seems to correspond with that of the partition coefficient of many drugs between octanol and water or a buffer. The apparent diffusion coefficient of DH and DNa in ethanol-aqueous solution was dependent on the ethanol concentration, i.e., it was related to the partition coefficient. The true diffusion coefficient of a lipid layer can be calculated by subtracting the partition coefficient from the apparent diffusion coefficient by changing the ethanol concentration.     

Microviscosity of hydroxypropylcellulose gels as a basis for prediction of drug diffusion rates

This study investigated the influence of the rheological properties of hydroxypropylcellulose (HPC) gels on the in vitro release of theophylline included in the gel at 0.2 g/l. Experiments were performed with six HPC varieties (mean molecular weight between 5x105 and 1.2x106, nominal viscosity between 100 and 4000 mPa.s) at concentrations of 0-2% (w/w). Theophylline diffusion coefficients at 37 degrees C ranged from 3.5x10-7 to 1.1x10-3 cm2/min, and were in all cases markedly higher than those predicted on the basis of gel macroviscosity as determined by capillary viscometry. In general, the theophylline diffusion coefficient declined exponentially with HPC concentration; in the case of the lowest-molecular-weight HPC, however, the diffusion coefficient remained constant to HPC concentrations of up to 0.8%, probably because of the high entanglement concentration of the HPC. Gel microviscosities as determined by dynamic light scattering (DLS) with latex microspheres (162 nm diameter) were considerably lower than the macroviscosities determined by capillary viscometry, and similar to microviscosities estimated on the basis of theophylline diffusion. Nevertheless, macroviscosity was correlated with microviscosity, suggesting that it is of value for approximate estimates of rates of diffusion of theophylline from HPC gels.     

氧化苦参碱的理化常数

目的测定氧化苦参碱的溶解度、解离常数(pKa)、油水分配系数(P)等理化常数,指导药物剂型的合理设计。方法按《中华人民共和国药典》中溶解度的测定方法测定氧化苦参碱在不同溶剂中的近似溶解度;采用电位滴定法、分光光度指示剂法测定氧化苦参碱的pKa值;采用摇瓶法测定氧化苦参碱在不同pH下的表观油水分配系数。结果氧化苦参碱在水、0.15 mol.L-1柠檬酸、0.15 mol.L-1碳酸钠溶液、甲醇、氯仿中溶解良好,在质量分数为20%的氢氧化钠溶液、石油醚和乙酸乙酯中溶解度都很低;电位滴定法、分光光度指示剂法测得的氧化苦参碱pKa分别为6.98、6.71;氧化苦参碱表观油水分配系数随着pH值的增加而增加,其真实油水分配系数为0.2。结论氧化苦参碱是一个亲水性很强的弱碱性药物。     

Effect of pH on in vitro permeation of ondansetron hydrochloride across porcine buccal mucosa

The influence of drug concentration, pH in donor chamber, and 1-octanol/buffer partition coefficient on transbuccal permeation of ondansetron hydrochloride (pKa, 7.4) across porcine buccal mucosa was studied by using an in-line Franz type diffusion cell at 37 degrees C. The pH was adjusted to several values and the solubility of the drug in different pH was measured. Solubility of ondansetron hydrochloride decreases with increasing pH. The permeability of the drug was evaluated at different donor pH and drug concentrations. Permeability of un-ionized (Pu) and ionized (Pi) species of drug was calculated by fitting the data to a mathematical model. The steady state flux increased linearly with the donor concentration (r2 = 0.9843) at pH 7.4. The permeability coefficient and the partition coefficient of the drug increased with increasing pH. The values of Pu and Pi were 4.86 x 10(-6) cm/sec and 7.18 x 10(-7) (c)m/sec, respectively. The observed permeability coefficients and the permeability coefficients calculated from the mathematical model at various pH showed good linearity (r2 = 0.9799). The total permeability coefficient increased with increasing the fraction of un-ionized form of the drug. The drug permeated through buccal mucosa by a passive diffusion process. The non-ionized species of drug penetrated well through buccal mucosa and the permeation was a function of pH. Transbuccal delivery is a potential route for the administration of ondansetron hydrochloride.     

川芎嗪眼用脂质体温敏凝胶的制备及体内外特性评价

目的:制备川芎嗪眼用脂质体温敏凝胶,考察其体内外特性.方法:采用硫酸铵梯度法制备川芎嗪脂质体,以正交试验优化制备工艺,并以泊洛沙姆P407为凝胶基质进一步制成温敏凝胶.采用无膜溶出模型对该凝胶的溶蚀性和体外释药特性进行研究;采用改良Franz扩散池考察其角膜透过性,并进一步测定角膜水化值;采用MTT法评价该凝胶对人角膜...     

Release of flurbiprofen from poloxamer 407 gel

Release rates of flurbiprofen from transdemal gels made of poloxamer 407 were evaluated using a membraneless diffusion cell in order to study the effects of formulation variables on flurbiprofen release such as poloxamer 407 (17.5–25%), drug (0.1–1.0%), ethanol (10–20%), PG or PEG 300 (5–15%) concentrations and gel pH (3–7). Isopropyl myristate was employed as a receptor medium for the drug released from the gel. The diffusion coefficient of flurbiprofen decreased linearly as the amount of poloxamer 407 and the drug in the gel increased. The release rate of flurbiprofen was gel pH-dependent and the diffusion coefficient of the drug in the gel increased as the pH of the gel increased. The addition of more ethanol in the gel increased the drug release, resulting from the increase of the thermodynamic activity of the drug in the aqueous phase of the gel. However, the concentration effects of PG and PEG 300 on the release rate of flurbiprofen were negligible over the concentration range used.     

Gastrointestinal absorption enhancement of insulin by administration of enteric microspheres and SNAC to rats

The preparation and characteristics of insulin enteric microspheres (EMS) were studied and the gastrointestinal absorption enhancement of insulin by co-administering EMS with sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC) was determined. The w/o/w and o(1)/o(2) emulsion solvent evaporation methods were used to prepare insulin-hydroxypropyl methylcellulose phthalate (HPMCP) EMS. High-performance liquid chormatography determined the drug loading, entrapment efficiency, stability to pepsin, and drug dissolution rate in hydrochloric acid solution (pH 1.2) and phosphate buffer solution (pH 6.8). The hypoglycaemic effect was studied by orally administrating the insulin EMS and SNAC to rats. The particle size of EMS (o(1)/o(2)) and EMS (w/o/w) was about 500 and 30 micro m respectively, and drug loading was 7 and 3% respectively. After being incubated with 18 micro g/mL pepsin solution (pH 1) at 37 degrees C, only 20% of insulin in EMS (o(1)/o(2)) was digested within 4 h, while 60% of the insulin in EMS (w/o/w) was digested within 1 h. In hydrochloric acid solution (pH 1.2), EMS (o(1)/o(2)) had less drug dissolution than EMS (w/o/w). In phosphate buffer solution (pH 6.8), the entire drug release time of EMS (o(1)/o(2)) and EMS (w/o/w) was 75 and 10 min, respectively. After orally administering with SNAC, EMS (o(1)/o(2)) could decrease the blood glucose level of rats remarkably and maintain the hypoglycaemic effect for 4 h, while EMS (w/o/w) had just a weakly hypoglycaemic effect. The results showed that the characteristics-optimized EMS, i.e. EMS (o(1)/o(2)) incorporating SNAC, could enhance insulin absorption significantly in the gastrointestional tract by taking advantage of both protection from enzyme degradation and improvement of drug permeability.     

Magnetic resonance imaging study of the transport phenomena of solvent into the gel layer of hypromellose matrices containing tetracycline hydrochloride

Magnetic resonance imaging was used to study the diffusion of a water solution of hydrochloric acid into hypromellose (hydroxypropylmethylcellulose) matrices. Spatially resolved information was obtained about the self-diffusion coefficient and spin-spin relaxation time of solvent protons in the gel layer of hypromellose matrices loaded with different amounts of tetracycline hydrochloride. The data showed the influence of the drug concentration on the diffusion and spin-spin relaxation. Higher drug concentrations in the hypromellose matrix led to greater swelling of the matrix and faster diffusion of the water molecules inside the gel layer of the polymer. The observed differences between the radial and axial diffusion were interpreted in terms of the stresses imposed in the axial direction during the compression of the samples. The spin-spin and diffusion profiles indicated that the diffusion of a water solution of hydrochloric acid into hypromellose, pure and loaded with different amounts of tetracycline hydrochloride, was characterized as a Case II mechanism.     

Poly(acrylamide-co-monoethyl Itaconate) Hydrogels as Devices for Cytarabine Release in Rats

This study has tested the application of three different copolymeric poly(acrylamide-comonoethyl itaconate; A/MEI) hydrogels, 90A/10MEI, 75A/25MEI and 60A/40MEI, on the release of cytarabine (ara-C). The drug was incorporated in gels by placing it in the polymerization feed mixture and discs loaded with 5–50 mg ara-C were obtained. The amount of swelling at equilibrium in saline solution (NaCl, 0.9% w/w) was between 78 and 82% w/w, depending on the composition of the copolymer. The diffusion studies followed Fick's second law. The diffusion coefficients for swelling of the gels were between 9.30 times 10^?11 m² s^?1 and 37.42 times 10^?11 m² s^?1; those for release of ara-C were between 3.42 times 10^?11 m² s^?1 and 10.25 times 10^?11 m² s^?1. The activation energies for swelling were in the range 16.60± 2.59-21.85± 1.78 kJ mol^?1; those for ara-C release were 28.13±3.1–29.7±4.6 kJ mol^?1. To determine the applicability of these copolymers, 75A/25MEI gel was subcutaneously implanted in rats and the plasma concentration of the drug was determined by high-performance liquid chromatography. The concentration of ara-C in plasma (range 17.67±5.68-10.76±2.15 μg mL^?1) was maintained during the first stages (2–8 h) and no drug was detected after 32 h. This route of administration was compared with intraperitoneal injection of the drug. In conclusion, ara-C can be incorporated in hydrogels and released in a pharmacologically active form. The concentration of ara-C in plasma is maintained for long enough to improve therapeutic results.     

Penetration-enhancing effect of ethanolic solution of menthol on transdermal permeation of ondansetron hydrochloride across rat epidermis

The aim of this investigation was to study the effect of an ethanol-water solvent system and ehtanolic solution of menthol on the permeation of ondansetron hydrochloride across the rat epidermis in order to select a suitable ethanol-water vehicle and optimal concentration of menthol for the development of a transdermal therapeutic system. The solubility of ondansetron hydrochloride in ethanol, water and selected concenetrtaion of ethanol-water vehicles (20:80 v/v, 40:60 v/v and 60:40 v/v) was determined. The effect of these solvent vehicles, containing 1.5% w/v of ondansetron hydrochloride, on the in vitro permeation of the drug was studied across the rat epidermis. The highest permeation was observed from 60% v/v of ethanol-water vehicle that showed highest solubilty. Hence, the hydroxypropyl cellulose (HPC) (2% w/w) gel formulations containing 1.5% w/w of ondansetron hydrochloride and selected concentrations of menthol (0, 2, 4, 8 and 10% w/w) were prepared using 60% v/v of ethanol-water vehicle, and subjected to in vitro permeation of the drug across rat epidermis. The transdermal permeation of ondansetron hydrochloride was enhanced markedly by the addition of menthol to HPC gel drug reservoir formulations. A maximum flux of ondansetron hydrochloride (77.85 ± 2.85 μ g/cm^2.h) was observed with a mean enhancement ratio of 13.06 when menthol was incorporated at a concentration of 8% w/w in HPC gels. However, there was no significant increase in the drug flux with 10% w/w menthol when compared to that obtained with 8% w/w of menthol in HPC gel formulations. The results suggest that 2% w/w HPC gel drug reservoir formulation, prepared with 60% v/v ethanol-water, containing 8% w/w of menthol provides an optimal transdermal permeation of ondansetron hydrochloride.