Formulation and In Vitro Evaluation of Mucoadhesive Sustained Release Gels of Phytoestrogen Diarylheptanoids from Curcuma comosa for Vaginal Delivery.

Diarylheptanoids (DAs) characterized by a 1,7-diphenylheptane structural skeleton are considered a novel class of phytoestrogens. The DAs available in Curcuma comosa Roxb. (C. comosa) extract demonstrated significant estrogenic activities both in vitro and in vivo. This study aimed to develop and comprehensively evaluate a mucoadhesive vaginal gel for the sustained release of DAs. Different mucoadhesive polymers as gelling agents were investigated. C. comosa ethanolic crude extract was used as a source of DAs. All C. comosa gels were light brown homogeneous with pH within 4.4-4.6. Their flow behaviors were pseudoplastic with a flow behavior index of 0.18-0.38. The viscosity at a low shear rate varied from 6.2 to 335.4 Pa·s. Their mechanical and extrudability properties were associated well with rheological properties. Polycarbophil (PCP):hydroxypropyl methylcellulose (HPMC) blends had a higher mucoadhesiveness to porcine vaginal mucosa than those of PCP-based or HPMC-based gels. All C. comosa gels exhibited a sustained, zero-order DA release pattern over 72 h. Korsmeyer and Peppas equation fitting indicated a non-Fickian, case II transport release mechanism. C. comosa gels had good physical and chemical stability under low-temperature storage for up to 12 months. PCP:HPMC-based mucoadhesive gels could be a proper delivery system for vaginal administration of DAs.

Preparation and Evaluation of Directly Compressible Orally Disintegrating Tablets of Cannabidiol Formulated Using Liquisolid Technique.

This study demonstrated the implementation of a liquisolid technique to formulate directly compressible orally disintegrating tablets (ODTs). Cannabidiol (CBD), a hydrophobic cannabinoid, was prepared as a liquisolid powder using microcrystalline cellulose-colloidal silicon dioxide as a carrier-coating material. Different liquid vehicles differing in their volatility, hydrophilicity, and viscosity were investigated. Each of the CBD-ODTs comprised CBD liquisolid powder (10 mg CBD), superdisintegrant, flavors, lubricant, and filler. The physical mixture (PM) ODT was prepared as a control. Ethanol-based ODTs (CBD-EtOH-ODTs) had comparable tablet properties and stability to CBD-PM-ODTs. ODTs with nonvolatile-vehicle-based liquisolid powder had lower friability but longer disintegration times as compared with CBD-PM-ODTs and CBD-EtOH-ODTs. Compression pressure influenced the thickness, hardness, friability, and disintegration of the ODTs. With a suitable compression pressure to yield 31-N-hardness-ODTs and superdisintegrant (4-8%), CBD-ODTs passed the friability test and promptly disintegrated (≤25 s). Times to dissolve 50% of CBD-PM-ODTs, CBD-EtOH-ODTs, and nonvolatile-vehicle-based CBD-ODTs were 10.1 ± 0.7, 3.8 ± 0.2, and 4.2 ± 0.4-5.0 ± 0.1 min, respectively. CBD-EtOH-ODTs exhibited the highest dissolution efficiency of 93.5 ± 2.6%. Long-term and accelerated storage indicated excellent stability in terms of tablet properties and dissolution. Nonvolatile-vehicle-based CBD-ODTs exhibited a higher percentage of remaining CBD. This study provides useful basic information for the development of ODT formulations using a liquisolid technique application.

In Vitro Release, Mucosal Permeation and Deposition of Cannabidiol from Liquisolid Systems: The Influence of Liquid Vehicles.

This work investigated the influence of liquid vehicles on the release, mucosal permeation and deposition of cannabidiol (CBD) from liquisolid systems. Various vehicles, including EtOH, nonvolatile low- and semi-polar solvents, and liquid surfactants, were investigated. The CBD solution was converted into free-flowing powder using carrier (microcrystalline cellulose) and coating materials (colloidal silica). A physical mixture of the CBD and carrier-coating materials was prepared as a control. The non-crystalline state of CBD in the liquisolid systems was confirmed using XRD, FTIR and SEM studies. The CBD liquisolid powder prepared with volatile and nonvolatile solvents had a better CBD release performance than the CBD formed as the surfactant-based and control powders. The liquisolid systems provided the CBD permeation flux through porcine esophageal mucosa ranging from 0.68 ± 0.11 to 13.68 ± 0.74 µg·cm-2·h-1, with the CBD deposition levels of 0.74 ± 0.04 to 2.62 ± 0.30 µg/mg for the dry mucosa. Diethylene glycol monoethyl ether showed significant CBD permeation enhancement (2.1 folds) without an increase in mucosal deposition, while the surfactants retarded the permeation (6.7-9.0 folds) and deposition (1.5-3.2 folds) significantly. In conclusion, besides the drug release, liquid vehicles significantly influence mucosal permeation and deposition, either enhanced or suppressed, in liquisolid systems. Special attention must be paid to the selection and screening of suitable liquid vehicles for liquisolid systems designed for transmucosal applications.

Mucosal Delivery of Cannabidiol: Influence of Vehicles and Enhancers.

In this study, the mucosal permeation and deposition of cannabidiol (CBD) with neat and binary vehicles were investigated. Permeation experiments were performed using static diffusion cells coupled with fresh porcine esophageal mucosa. The CBD-vehicle solutions were applied at a fixed dose (~5 mg/cm2), and the corresponding permeation parameters were calculated. In neat vehicles, the permeation flux (Jss) ranged from 0.89 ± 0.15 to 179.81 ± 23.46 µg·cm-2·h-1, while the CBD deposition ranged from 11.5 ± 1.8 to 538.3 ± 105.3 µg·cm-2. Propylene glycol (PG) and diethylene glycol monoethyl ether (DEGEE) yielded the highest permeability (Ps) and CBD deposition, while medium-chain triglycerides (MCT) yielded the lowest Ps and deposition. This was due to the difference in apparent partition coefficient (K), which is related to the solubility of CBD in the vehicle. The PG:DEGEE binary vehicle boosted Jss (1.5-1.6 fold) and deposition (2.0-2.7 folds) significantly, compared to neat DEGEE. The combination of DEGEE with MCT dramatically enhanced Jss (11-44 fold) and deposition (1.6-4.7 fold). The addition of lipophilic enhancers, laurocapram, and oleic acid, to PG:DEGEE and DEGEE:MCT vehicles significantly reduced Jss (0.3-0.7 fold) and deposition (0.4-0.8 fold) while nerolidol had no effect. These permeation reductions were found to be related to modification of the K and/or diffusivity values. This study provides useful basic information for the development of CBD formulations intended for transmucosal delivery.

Application of a liquisolid technique to cannabis sativa extract compacts: Effect of liquid vehicles on the dissolution enhancement and stability of cannabinoids.

This work describes the application of liquisolid technique to enhance cannabinoid dissolution from Cannabis sativa L. (CS) compacts. Effects of five vehicles, namely, volatile (ethanol) and nonvolatile (caprylocaproyl macrogolglycerides, polyethylene glycol 400, oleoyl macrogolglycerides and polysorbate 20) liquids, on tablet properties, dissolution and stability were investigated. The viscid oleoresin CS extract was mixed with vehicles before being transformed into free-flowing powder by the use of microcrystalline cellulose and colloidal silica as carrier and coating materials. Liquid vehicles had a nonsignificant effect on liquid load factor of CS extract. CS liquisolid compacts had acceptable tableting properties in terms of weight variation, friability, hardness, content uniformity and disintegration time. Different vehicles affected the hardness, disintegration, and wettability of CS compacts and thus the dissolution behaviors of cannabinoids to different extents. Dissolutions of cannabinoids from CS compacts were rate-limited by the disintegration process. Liquisolid formulations using nonvolatile liquids with low polarity or high hydrophilic-lipophilic balance yielded more than 90% cannabinoid dissolution. Stability studies revealed nonsignificant changes in tablet characteristics, cannabinoid content and dissolutions of CS compacts when stored at 5 ± 3 °C for 3 months. This work presents a general concept of how to successfully formulate CS extract with cannabinoid dissolution enhancement characteristics.

Modification of release and penetration behavior of water-soluble active ingredient from ball-milled glutinous starch matrix via carboxymethylcellulose blending.

This present work describes the possible advantages of carboxymethylcellulose (CMC) blending with ball-milled glutinous starch (BMGS) on the modification of release and penetration of model water-soluble active ingredient, lidocaine hydrochloride, from the blended matrix. The 20-67% CMC mass containing CMC-BMGS matrices were fabricated by casting the aqueous dispersion of CMC-BMGS onto the tray and oven-dried. BMGS and CMC were compatible as revealed by SEM and ATR-FTIR. Irrespective of the CMC mass, all CMC-BMGS matrices showed comparable matrix mass, thickness, moisture content, moisture absorption as well as mechanical and mucoadhesive properties. The surface pH of CMC-BMGS tended to increase with the CMC mass. Depends on CMC mass, matrix properties, release, and penetration rates were modulated significantly. CMC had shown a substantial role in the swelling and erosion behaviors of BMGS films, and thus modulated the release and penetration significantly. The release and penetration mechanisms of active ingredient from the CMC-BMGS matrices were Fickian diffusion-controlled, with rates of release and penetration ranging from 2.05 ± 0.21 to 7.55 ± 1.08%/min½, and from 3.48 ± 0.28 to 8.04 ± 0.64 µg/cm2/min½, respectively. The capability of CMC-BMGS matrices as mucoadhesive delivery systems to provide sustained delivery of water-soluble active ingredients was disclosed.

Permeation, stability and acute dermal irritation of miroestrol and deoxymiroestrol from Pueraria candollei var. mirifica crude extract loaded transdermal gels.

In this study, permeation behaviors and chemical stability of miroestrol and deoxymiroestrol from Pueraria candollei var. mirifica (PM), Thai traditional medicine, crude extract containing transdermal gels were firstly evaluated. Three different PM extract containing gels were formulated, including hydroalcoholic and microemulsion gels using carbomer, and silicone gel using silicone elastomer. In vitro permeation through porcine ear skin demonstrated that the flux and 24 h cumulative permeation of miroestrol and deoxymiroestrol were in the order of hydroalcoholic > silicone > microemulsion gels. Hydroalcoholic gel provided the highest partition coefficient from gel onto skin, and thus the skin permeability coefficient. After 24 h permeation, no miroestrol and deoxymiroestrol remained deposited in the skin. Accelerated study using heating-cooling revealed insignificant difference between the remaining percentages of miroestrol and deoxymiroestrol in aqueous and non-aqueous based gels. Long-term stability study showed that miroestrol contents remained constant for 90 d and 30 d under 5 ± 3 °C and 30 ± 2 °C, 75 ± 5%RH, respectively; whereas the percentage of deoxymiroestrol decreased significantly after 30 d storage, irrespective of storage conditions. Acute dermal irritation test on New Zealand White rabbits showed that PM hydroalcoholic gels were non-irritant, with no signs of erythema or oedema.[Figure: see text].

Modified glutinous rice starch-chitosan composite films for buccal delivery of hydrophilic drug.

The fabrication and characterization of ball-milling modified glutinous rice starch (MGRS):chitosan (CS) composite films were demonstrated. Effect of CS ratios (2:1, 1:1, 1:2 MGRS:CS) on the film properties was investigated. Lidocaine hydrochloride was used as a model hydrophilic drug. ATR-FTIR confirmed hydrogen bond formation between MGRS and CS. XRD indicated an amorphous state of all fabricated films. The uniform and comparable thickness, weight, and drug contents of all fabricated films were obtained. The presence of CS did not affect the mucoadhesiveness of MGRS films. The increase in tensile strength and decreases in elongation and folding endurance were observed with 1:2 MGRS:CS films. The film swelling and drug release decreased with the CS ratio. Drug permeation across porcine mucosa indicated the enhancement effect of CS, whereby the permeation flux of 1:2 MGRS:CS composite increased by 3 folds. In conclusion, the MGRS:CS composite could be useful for buccal delivery of hydrophilic drug.

Physical modification of Thai rice starch and its application as orodispersible film former.

The objective of this study was to investigate the application of the physically modified rice starch (MRS) produced by alcoholic-alkaline (MRS-AA) and planetary ball-milling (MRS-BM) methods as an ODF film former. Rice starch was isolated from Thai rice grain. XRD and ATR-FTIR results confirmed crystallinity loss of MRS. MRS-AA exhibited prominently the greater swelling capacity, whereas MRS-BM exhibited prominently the greater cold water solubility. The starch-based orodispersible films (ODFs) with acceptable film and mechanical properties were successfully prepared using solvent casting method. MRS-based ODFs exhibited the greater flexible behaviors but lower disintegration time compared with the native system. Desloratadine loaded MRS-BM-based ODFs disintegrated within 62.3 ±â€¯23.1 s, with more than 95% dissolution within 10 min. In conclusion, the ball-milling treatment resulted in the preferable MRS suitable for use as an ODF film former. This study therefore provides a glimpse into the use of physically modified starch as an ODF film former.

Thai glutinous rice starch modified by ball milling and its application as a mucoadhesive polymer.

This study aimed to investigate physicochemical properties and potential application as a mucoadhesive polymer of Thai glutinous rice starch modified by planetary ball milling. XRD and ATR-FTIR results indicated a reduction in crystallinity of starch after ball milling. Different ball milling times, ranging from 5 to 45 min, resulted in modified glutinous rice starch (MGRS) with different levels of crystallinity loss, and therefore varying degrees of cold water solubility, swelling capacity, and gelatinized dispersion viscosity. Investigation of mucoadhesive properties using Texture Analyzer with porcine mucosa demonstrated that MGRS tablets exhibited greater mucoadhesive abilities compared to hydroxypropyl methylcellulose tablets, but weaker than those of sodium carboxymethylcellulose tablets. Tablets made of 15-min-milled MGRS had comparable tableting, swelling and mucoadhesiveness, but lower erosion compared to 45-min-milled MGRS. Conclusively, ball milling treatment could successfully induce the mucoadhesive properties of Thai glutinous rice starch and expand its application as mucoadhesive polymer.

Preparation of Curcuma comosa tablets using liquisolid techniques: In vitro and in vivo evaluation.

Curcuma comosa (C. comosa) is a Thai medicinal herb that provides numerous pharmacologic activities due to its estrogen-like action. This study aimed to investigate the use of liquisolid technique to prepare tablets containing oleoresin-like crude extract of C. comosa, and to improve the dissolution profiles of its major compounds, diarylheptanoids (DAs). Free flowing powders of C. comosa extract were obtained by adsorption onto solid carriers, microcrystalline cellulose, with colloidal silica as coating material. FTIR results ruled out possible interactions between C. comosa extract and excipients. The results indicated that all of liquisolid tablets met the USP requirements. The release of DAs were significantly increased through liquisolid formulations, compared to crude extract. By decreasing the ratio of carrier to coating from 20 to 10, an improvement in dissolution rate was observed. Addition of additives - namely polymer (polyvinyl pyrrolidone) and/or nonvolatile liquid (propylene glycol) affected tablet properties which involved longer disintegration time and lower DA dissolution. Optimized C. comosa liquisolid formulation was prepared in a carrier to coating ratio of 10 without additives. Stability studies showed that physical properties of liquisolid tablet were not affected by aging, but percent remaining and dissolution profiles of DAs were influenced by storage temperature. In vivo pharmacokinetic behavior of the optimized C. comosa liquisolid tablets was investigated following a single oral administration to rabbits. The results proved that the method used for preparation of liquisolid led to C. comosa tablets with low variation in content uniformity and tablet properties, as well as enhanced dissolution behavior.

Development and evaluation of topical films containing phytoestrogenic diaryheptanoids from Curcuma comosa extract.

RATIONAL: Phytoestrogens have been found to delay signs of skin aging in post-menopausal women, in a way similar to the effects of estrogens. Diarylheptanoids from a rhizome of traditional Thai herb named Curcuma comosa is considered to be a novel class of phytoestrogens. OBJECTIVES: The aims of this study were to prepare effective topical films using mixed types and vary ratios of hydrophobic (Eudragit RL, Eudragit RS, and Eudragit NE) and hydrophilic polymer (hydroxylpropyl methycellulose, HPMC) with Transcutol as a permeation enhancer for delivery of diarylheptanoids to improve signs of skin aging in post-menopausal women. MATERIAL AND METHODS: Topical films were characterized for their physical and mechanical properties. In vitro release, skin permeation and accumulation were evaluated using Franz diffusion cell and the concentrations of diarylheptanoids were determined using high-performance liquid chromatography. RESULTS: The combined formulations between HPMC and Eudragit NE showed the satisfactory physical and mechanical properties, and also provided the highest amount of drug released compared to Eudragit RL and Eudragit RS. When the proportion of HPMC amount in the polymer matrix increased, the cumulative drug release also increased (HPMC: Eudragit NE 6:4 > 5:5 > 4:6). Moreover, they provided a high accumulation of diarylheptanoids within skin when using transcutol as a permeation enhancer. CONCLUSION: The obtained data provided the skin permeation and accumulation behavior of diarylheptanoids, indicating the feasibility of a skin delivery of the C. comosa extract. The developed films might be topically used as an alternative therapy for protection of skin aging in peri and post-menopausal women.

Effects of Vehicles and Enhancers on the Skin Permeation of Phytoestrogenic Diarylheptanoids from Curcuma comosa.

Curcuma comosa (C. comosa) is widely used in traditional medicine as a dietary supplement for health promotion in postmenopausal women in Thailand. It contains several diarylheptanoids, which are considered to be a novel class of phytoestrogens. However, the diarylheptanoids isolated from the plant rhizome are shown to have low oral bioavailability and faster elimination characteristics. The aim of this study was to investigate the permeation behavior of the active compounds of diarylheptanoids. The effects of binary vehicle systems and permeation enhancers on diarylheptanoids permeation and accumulation within the skin were studied using side-by-side diffusion cells through the porcine ear skin. Among the tested binary vehicle systems, the ethanol/water vehicle appeared to be the most effective system for diarylheptanoids permeation with the highest flux and shortest lag time. The presence of transcutol in the vehicle system significantly increased diarylheptanoid's permeation and accumulation within the skin in a concentration-dependent manner. Although the presence of terpenes in formulation decreased the flux of diarylheptanoids, it raised the amount of diarylheptanoids retained within the skin substantially. Based on the feasibility of diarylheptanoid permeation, C. comosa extract should be further developed into an effective transdermal product for health benefits and hormone replacement therapy.

Optimization of minoxidil microemulsions using fractional factorial design approach.

The objective of this study was to apply fractional factorial and multi-response optimization designs using desirability function approach for developing topical microemulsions. Minoxidil (MX) was used as a model drug. Limonene was used as an oil phase. Based on solubility, Tween 20 and caprylocaproyl polyoxyl-8 glycerides were selected as surfactants, propylene glycol and ethanol were selected as co-solvent in aqueous phase. Experiments were performed according to a two-level fractional factorial design to evaluate the effects of independent variables: Tween 20 concentration in surfactant system (X1), surfactant concentration (X2), ethanol concentration in co-solvent system (X3), limonene concentration (X4) on MX solubility (Y1), permeation flux (Y2), lag time (Y3), deposition (Y4) of MX microemulsions. It was found that Y1 increased with increasing X3 and decreasing X2, X4; whereas Y2 increased with decreasing X1, X2 and increasing X3. While Y3 was not affected by these variables, Y4 increased with decreasing X1, X2. Three regression equations were obtained and calculated for predicted values of responses Y1, Y2 and Y4. The predicted values matched experimental values reasonably well with high determination coefficient. By using optimal desirability function, optimized microemulsion demonstrating the highest MX solubility, permeation flux and skin deposition was confirmed as low level of X1, X2 and X4 but high level of X3.

Skin deposition and permeation of finasteride in vitro: effects of propylene glycol, ethanol and sodium lauryl sulfate.

The objective of this study was to investigate the effects of propylene glycol (PG), ethanol (EtOH) and sodium lauryl sulfate (SLS) on the in vitro deposition and permeation of finasteride (FNS). A side-by-side diffusion cell mounted with a pig ear skin and a saturated solution of FNS in PG (10, 20% v/v), EtOH (10, 20% v/v) or SLS (0.5, 1% w/v) vehicles were used. Incorporation of PG, EtOH or SLS caused a significant increase in FNS solubility both in the solution and on the skin with SLS > EtOH > PG. The results obtained from skin deposition studies showed that the FNS deposition rate and time increased in the same order as that of the solubility. The deposition kinetics of FNS solubilized in PG, EtOH and SLS vehicles followed either zero-order, square-root-of-time or pseudo-first-order kinetic models depending on the type and concentration of the enhancer. The permeation studies demonstrated that FNS permeation fluxes were enhanced only by EtOH vehicles. These results suggest that PG and SLS could be used as deposition enhancers, while EtOH could be the effective permeation enhancer of FNS. The obtained results can be used as the considerable insights for formulating the topical and transdermal products of FNS.

A monolithic drug-in-adhesive patch of methoxyflavones from Kaempferia parviflora: in vitro and in vivo evaluation.

The aim of this study was to design and develop a suitable monolithic drug-in-adhesive type patch of methoxyflavones from Kaempferia parviflora (K. parviflora) using acrylic polymer Durotak(®) 87-2852. The absence of interaction between components in K. parviflora extract and the adhesive polymer was confirmed by attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). Thirteen K. parviflora patches with different extract loading and permeation enhancers were prepared by the solvent evaporation technique. All formulations showed good physicochemical properties, good stability and satisfactory adhesive properties. The effect of K. parviflora loading and permeation enhancers on methoxyflavones transport across porcine ear skin was also evaluated. The permeation of methoxyflavones increased with the amount of K. parviflora. Among the permeation enhancers investigated, oleic acid increased permeation flux of total methoxyflavones by 1.25 fold compared to the control; whereas menthol shortened the lag time. When oleic acid and menthol were combined, the maximum flux of methoxyflavones and shortest lag time were observed, suggesting a synergistic effect of menthol with oleic acid. The optimal patch formulation contained 15% K. parviflora, 3% oleic acid and 3% of menthol, and this was evaluated via an in vivo pharmacokinetic study using rats. The maximum plasma drug concentration (Cmax) of total methoxyflavones was 218.08ng/ml with Tmax at 8h. The concentrations of methoxyflavones in plasma continued to increase until the end of the experiment, indicating a sustained release into the systemic circulation.

Transdermal permeation of Kaempferia parviflora methoxyflavones from isopropyl myristate-based vehicles.

Kaempferia parviflora (K. parviflora) rhizomes have long been used in traditional folk medicines and as general health-promoting agents. Several biological activities of K. parviflora, especially its anti-inflammatory effect, are due to its major constituents, methoxyflavones. However, the oral bioavailability of these methoxyflavones has been shown to be low. The aim of this study was to investigate the permeation behaviors of K. parviflora methoxyflavones from isopropyl myristate (IPM)-based vehicles. We studied the effects of ethanol and propylene glycol (PG) as the hydrophilic, solvent-type vehicles as well as fatty acids as the permeation enhancers. A permeation experiment was performed in vitro, using side-by-side diffusion cells through the full thickness of pig ear skin. The solubility and permeation of methoxyflavones were able to be modified by choice and ratio of vehicles. The ethanol/IPM vehicle was shown to be more effective in enhancing the solubility and permeation of methoxyflavones when compared to the PG/IPM vehicle. Regarding an optimal balance between solubility or affinity to vehicle and skin to vehicle partition coefficient, the ethanol/IPM vehicle in the ratio of 1:9 maximized the flux. Among the investigated fatty acids, oleic acid showed the greatest enhancing effect on the permeation of methoxyflavones, indicating that saturated fatty acids are less effective than unsaturated fatty acids. Long chain fatty acids increased diffusion coefficient parameter and shortened the lag time. The number of carbon atoms and double bonds of fatty acids did not show direct relation to the profile of permeation of methoxyflavones.

Preparation and evaluation of diltiazem hydrochloride diffusion-controlled transdermal delivery system.

The objective was to investigate the suitable polymeric films for the development of diltiazem hydrochloride (diltiazem HCl) transdermal drug delivery systems. Hydroxypropyl methylcellulose (HPMC) and ethylcellulose (EC) were used as hydrophilic and hydrophobic film formers, respectively. Effects of HPMC/EC ratios and plasticizers on mechanical properties of free films were studied. Effects of HPMC/EC ratios on moisture uptake, in vitro release and permeation through pig ear skin of diltiazem HCl films were evaluated. Influence of enhancers including isopropyl myristate (IPM), isopropyl palmitate (IPP), N-methyl-2-pyrrolidone, oleic acid, polyethylene glycol 400, propylene glycol, and Tween80 on permeation was evaluated. It was found that addition of EC into HPMC film produced lower ultimate tensile strength, percent elongation at break and Young's modulus, however, addition of EC up to 60% resulted in too hard film. Plasticization with dibutyl phthalate (DBP) produced higher strength but lower elongation as compared to triethyl citrate. The moisture uptake and initial release rates (0-1 h) of diltiazem HCl films decreased with increasing the EC ratio. Diltiazem HCl films (10:0, 8:2 and 6:4 HPMC/EC) were studied for permeation because of the higher release rate. The 10:0 and 8:2 HPMC/EC films showed the comparable permeation-time profiles, and had higher flux values and shorter lag time as compared to 6:4 HPMC/EC film. Addition of IPM, IPP or Tween80 could enhance the fluxes for approx. three times while Tween80 also shorten the lag time. In conclusion, the film composed of 8:2 HPMC/EC, 30% DBP and 10% IPM, IPP or Tween80 loaded with 25% diltiazem HCl should be selected for manufacturing transdermal patch by using a suitable adhesive layer and backing membrane. Further in vitro permeation and in vivo performance studies are required.