Drug Permeation Rate Research Articles

Amphiphilic disodium glycyrrhizin as a co-former for ketoconazole co-amorphous systems: Biopharmaceutical properties and underlying molecular mechanisms

Co-amorphous systems (CAMs) have been extensively investigated to improve the dissolution of hydrophobic drugs. However, drug precipitation during the storage or dissolution of CAMs has still been a major challenge. Here, disodium glycyrrhizin (Na2GA) was first used as a co-former in CAMs based on its multiple hydroxyl groups and amphiphilic structure. Ketoconazole (KTZ), a BCS class II drug, was selected as a model drug. KTZ-Na2GA CAMs at mass ratios of 1:1, 1:2.5, 1:5 and 1:10 were prepared by the spray drying method and further characterised by PXRD and DSC. The 1:2.5, 1:5 and 1:10 groups exhibited significantly enhanced Cmax (all approximately 26.67-fold) and stable maintenance of supersaturation compared to the crystalline KTZ and the corresponding physical mixtures in non-sink dissolution tests, while the 1:1 group exhibited an unstable medium Cmax (all approximately 14.67-fold). The permeability tests revealed that the permeation rate of KTZ in KTZ-Na2GA CAMs under the concentration of Na2GA in solution above the critical micelle concentration (CMC) showed a significant downwards trend compared to that below CMC. The underlying molecular mechanisms were involved in molecular miscibility, hydrogen bond interactions, solubilisation and crystallisation inhibition by Na2GA. Pharmacokinetic studies demonstrated that the AUC0-∞ of KTZ in 1:1, 1:2.5, 1:5 and 1:10 groups were significantly higher than those of the crystalline KTZ group with 2.13-, 2.30-, 2.16- and 1.86-fold, respectively (p < 0.01). In conclusion, Na2GA has proven to be a promising co-former in CAMs to enhance hydrophobic drug dissolution and bioavailability. Its effect on intestinal permeation rate of drugs also deserves attention.

Up-to-date Combinational Polymeric Approaches for the Enhancement of Drug Absorption and Membrane Transductivity

Abstract: Many of the challenges concerning pharmaceutical compounds are involved in the tuning of their physical properties and controlled and targeted drug delivery, in order to acquire the optimum therapeutic effect. With these challenges in mind and with the recent emergence of advanced materials, various combinational polymeric approaches have been applied. The use of coordination polymers, which are hybrid inorganic-organic materials, consists of transition metals and multidentate organic ligands and have been proven to prolong the release and increase the drug permeation rate of active pharmaceutical ingredients (APIs). Another recent approach is the preparation of deformable polymeric nanoparticles (DPN) that require the physical incorporation of a lipid in a polymeric micelle, offering flexible and deformable phase properties. It has been shown that skin delivery efficiency could be increased due to this deformable phase. Enhanced skin permeation was also observed when TAT peptides were chemically attached to the DPNs. Other recent approaches, such as microarray patches, sustained release microspheres, nanoparticles coated with biological membranes, nanosponges, and lipid-based nanoparticles, modified by polymers, have also been able to improve the pharmacokinetic profiles of APIs and are also discussed in this paper.

Predicting skin permeation-enhancing effect of fixed oils using saturated to unsaturated fatty acid ratio content

Background: Transdermal drug delivery is non-invasive and advantageous as it improves patient compliance.&#x0D; Objective: This study evaluated the effect of varying ratios of saturated to unsaturated fatty acids in fixed oils on the permeation of ibuprofen across pig dorsal skin.&#x0D; Methods: The solubility of ibuprofen in soybean oil, theobroma oil, and shea butter (fixed oils) was evaluated and in vitro skin permeation studies were conducted using Franz diffusion cells.&#x0D; Results: A significant difference in permeability parameters, such as flux and effective skin permeability, in the different formulations was observed. Skin permeation depended on the ratio of saturated to unsaturated fatty acids. It also depended on the type and concentration of individual saturated and unsaturated fatty acids present in the fixed oils. The skin permeation of ibuprofen increased with an increasing ratio of palmitic acid (PA) to oleic acid (OA) concentrations. The highest flux was obtained in the theobroma oil formulation, with a PA:OA ratio of 0.78. The lowest flux was obtained in the shea butter formulation, with a PA:OA ratio of 0.09. The PA:OA ratio was 0.46 in the soybean oil formulation.&#x0D; Conclusion: These results suggest that the ratio of saturated to unsaturated fatty acids in fixed oils could be used as a model for predicting the rate of skin permeation of drugs in oil-based formulations. Depending on the desired rate of drug permeation, different combinations of the ratio of saturated to unsaturated fatty acids can be used in formulations for transdermal delivery.

Effect of ion pair strategy on transdermal delivery of guanfacine: Which factor dominates drug permeation?

Ion pair is an effective chemical approach to promoting drug transdermal permeation, and the traditional interpretation for its enhanced permeation effect is mainly attributed to counterions altering the physicochemical properties of the drug (lipophilicity, melting point, etc.). In this work, guanfacine (GFC), a non-stimulant for anti-attention deficit and hyperactivity disorder (ADHD), was used as a model drug, and several organic or inorganic acids were designed thereby successfully constructing ion pairs. The transdermal permeation ability of ion pairs through isolated porcine skin was observed and ranked as follows: guanfacine caprylate (GFC-CA) > GFC > guanfacine laurate (GFC-LA) > guanfacine fumarate (GFC-FA) > guanfacine hydrochloride (GFC-HA) > guanfacine palmitate (GFC-PA). The effect of key physicochemical properties (octanol–water partition coefficient, molecular volume, melting point) on the transdermal permeation rate of the model drug was analyzed in detail. In addition, GFC-CA was observed to alter the lipid structure of the skin, suggesting the traditional explanation of the action of ion pair may be inadequate and underrated, and ion pair may also enhance permeation by disrupting skin structure. The intriguing phenomenon is expected to provide a novel approach to achieving precise transdermal drug delivery.

The effect of anionic Eudragit polymers on drug supersaturation and in vitro permeation improvement

Objectives In the present study, Cinnarizine was selected as a weakly basic drug with poor aqueous solubility to investigate the supersaturation maintaining the ability of different types of anionic Eudragit polymers (Eudragits L100-55, L100 and S100). Furthermore, the interplay between polymer-mediated supersaturation maintenance and in vitro permeation enhancement was studied. Methods The effect of Eudragit polymers on the pH-induced supersaturation of Cinnarizine was examined under different pHs (6.4, 6.8 and 7.8). Moreover, the effect of Eudragit polymers on the permeation of Cinnarizine through the Caco-2 membrane was investigated. Results The aggregate size of Eudragit polymers in solution was determined and it was found that the size of polymer aggregate was bigger when lower pH or more hydrophobic polymer was used, which corresponded strongly with improved drug supersaturation. Based on the findings, hydrophobic Cinnarizine-polymer interactions seemed to be essential in determining the impact of Eudragit polymers on maintaining the Cinnarizine supersaturation. The permeation study demonstrated that the rate of drug permeation through the Caco-2 membrane increased in the presence of Eudragit polymers, but their effect on maintaining supersaturation was more significant than their effect on the drug permeation rate. Moreover, the highest level of Cinnarizine supersaturation observed in a non-permeation condition did not correlate with the optimal absorption in a permeation condition. Conclusion This study revealed that the integration of permeation and supersaturation assays is needed to reliably predict the impact of supersaturation maintenance by polymers on the absorption of poorly soluble drugs.

Micro-pillar tunnel stamp for enhanced transdermal delivery of topical drug formulations.

Dissolving microneedles (DMNs), despite their minimally invasive drug administration, face challenges in skin insertion and drug-loading capacity, which lead to less effective drug delivery. The micro-pillar tunnel stamp (MPTS) was designed to enhance the transdermal delivery efficacy of externally provided topical formulations via the creation of microchannels. The tunnel and canal of the MPTS enable the simultaneous application of DMNs and topical drugs. The application of micro-pillar-polycaprolactone (MP-PCL), which is a DMN made of a slowly dissolving polymer, exhibited a drug permeation rate 1.3-fold and 2.6-fold higher than that of micro-pillar-hyaluronic acid (MP-HA), a DMN made of a rapidly dissolving polymer, and the topical group, respectively. The base diameter of MP-PCL was set to 700 μm for maximized delivery efficacy, achieving 2.8-fold higher L-ascorbic acid accumulation than that of the topical group. In vivo analysis showed that, compared to topical administration, MPTS-delivered lidocaine had 5-fold greater permeation and the MPTS-delivered group showed 1.25-fold higher skin residual amount, confirming enhanced delivery. Thus, the optimized MPTS system can be presented as an attractive alternative to overcome the limitations of the existing MN systems such as incomplete insertion and limited drug-loading capacity, enhancing the delivery of topical formulations in the transdermal market. STATEMENT OF SIGNIFICANCE: We developed a micro-pillar tunnel stamp (MPTS) to enhance the delivery of externally provided topical formulations. The functional tunnel and canal of the MPTS enabled the simultaneous application of a dissolving microneedle (DMN) array insertion and administration of external topical drugs. Upon insertion, the DMNs created skin microchannels that allowed the externally administered drug to diffuse. DMNs were fabricated using polycaprolactone (PCL), a slowly dissolving polymer, to maintain their structure inside the skin and prolong the opening duration of the microchannels. This system achieved significantly improved delivery of topically administered external drugs via integration with slowly dissolving DMNs, while offering the possibility of its development as a universal delivery system for various topical pharmaceuticals.

DoE-based formulation, physicochemical properties, and anti-inflammatory investigation of a topical patch preparing by partially neutralized polyacrylate-based adhesive hydrogel

A capsaicin patch was formulated by optimizing the adhesion, the release behavior of the patch, and the pharmacological effect. The aims of study were to 1) apply the design of experiments approach for investigating the simultaneous effect of Viscomate (partially neutralized polyacrylate)-based adhesive, glycerin plasticizing excipient and permeation enhancers on patch adhesion, and the permeation rate of model drug (capsaicin) and then 2) compare the optimal formulation with the reference product (Wellpatch®, Metholatum, U.S.A.) in terms of pharmacological effect. The topical patch was prepared by casting the drug-loaded adhesive hydrogel on the backing layer. The adhesive ability of patches was determined by testing a 90° peel rig on a texture analyzer, and the permeation rate of capsaicin (CAP) through mouse skin was evaluated using Franz diffusion cells. The effects of these critical factors on patch adhesion, CAP flux, and permeation enhancer interaction with the stratum corneum were analyzed using ANOVA and ATR-FTIR/skin hydration tests, respectively. Accordingly, Viscomate (adhesion excipient) and glycerin (plasticizing excipient) had a significant impact on patch adhesion (p < 0.05). Meanwhile, N-methyl pyrrolidone, the permeation enhancer, had a better permeation rate and higher hydration level of the stratum corneum than did Transcutol. The partially neutralized polyacrylate-based optimal formulation had a higher permeation rate of CAP, equal adhesion and comparable anti-inflammatory effects to those of the reference product which was also in agreement with the analysis of anatomical images of tissue structure and inflammatory cells. This study successfully integrated DoE method, release behavior and pharmacological research to develop a stable and highly effective topical product containing capsaicin.

Development of In Vitro Evaluation System for Assessing Drug Dissolution Considering Physiological Environment in Nasal Cavity.

Estimating the dissolution behavior of a solid in the nasal mucus is challenging for solid dosage forms designed for the nasal application as the solid dissolves into nasal mucus and permeates through the mucosa. In the current study, the dissolution behavior of powders in the artificial nasal fluid was investigated using a 3D-printed chamber system to establish in vitro evaluation system for the dissolution of solid formulations that can simulate the intranasal environment in vivo. The dissolution rates of the five model drugs correlated with their solubility (r2 = 0.956, p &lt; 0.01). The permeation rate of drugs across the Calu-3 cell layers after powder application depends on the membrane permeability of the drug. An analysis of membrane permeability considering the dissolution of powders showed the possibility of characterizing whether the drug in the powder was dissolution-limited or permeation-limited. This suggests that critical information can be obtained to understand which mechanism is more effective for the improvement of drug absorption from powders. This study indicates that the elucidation of drug dissolution behavior into nasal mucus is an important factor for the formulation of nasal powders and that the in vitro system developed could be a useful tool.

Fabrication and Evaluation of Matrix Type Novel Transdermal Patch Loaded with Tramadol Hydrochloride

Transdermal drug delivery as a novel drug delivery system has become a major research interest to the scientists for its controlled drug release and improved patient compliance. This study was conducted to develop an optimized transdermal patch of tramadol hydrochloride using an appropriate amount of suitable polymers. It was also planned to control the drug permeation rate from the device to achieve a sustained release pattern. Several numbers of formulations were prepared by altering the amount of excipients. Physicochemical and biopharmaceutical parameters were checked to get the optimized formulation with desired characteristics. Fourier transform infrared spectroscopy results displayed no abnormal peaks and hence concluded that the drug and polymers were compatible with each other. The minimum standard deviation values of different physicochemical parameters assured that the method of preparation was skilled to develop patches with least intra-batch variability. A higher percentage of hydroxypropyl methylcellulose (HPMC) resulted in the greater tensile strength, moisture content and water vapor transmission rate of the patches. A high folding endurance value (>200) indicated the flexibility of the prepared patches and their integrity to the skin. The transdermal patches coded as F26 containing only HPMC polymer demonstrated the desired drug permeation rate (65.51%) within 12 hours through ex vivo permeation studies. The formulation coded as F26 was found to be the most optimized patch as it exhibited sustained drug permeation rate followed by higuchi diffusion kinetics, that also confirmed the capability of the formulation to exhibit matrix type drug delivery.

Enhancement of Drug Penetration Rate by Enriching Skin Hydration: A Novel Amalgamation of Microemulsion and Supersaturation

Background: The evolving need and facilitation of topical formulations have risen in the present era. Topical industries are continually striving to satisfy patients with newer and innovative products. However, dry skin is the critical factor contributing to drug penetration into the skin. Objective: The current research aims to develop cost-effective and commercially feasible industrial scale microemulsion of wheat germ oil to enrich skin hydration, enhancing the drug permeation rate. Methods: The Pseudo-ternary phase diagram was constructed for screening of microemulsion components. Wheat germ oil containing O/W microemulsion was prepared and evaluated for physicochemical parameters, thermodynamic stability study, globule size determination, enhancement of skin hydration, and skin permeation rate by ex vivo study. Results: The wheat germ oil containing microemulsion was prepared by incorporating tween 20 [surfactant] and ethanol [co-surfactant]. All physicochemical parameters were in the ideal range. Following the thermodynamic stability study, the TEM study showed globule size of optimized microemulsions in the range of 69.64 nm to 84.42 nm. The skin moisture tester showed a high hydration level for more than eight hours. An Ex vivo study revealed higher drug flux [Jss] of Pomegranate peel Extract [17.99 μg/cm2/h] with an enhancement ratio of 1.69. Conclusion: The topical formulation application has become challenging for researchers due to the skin's dryness and lower water content. However, the developed WGO microemulsion aids more penetration and is helpful in achieving higher drug flux. In addition, it is a cost-effective, easy to prepare, and patient-friendly drug delivery system.

Formulation development of anti-rheumatoid gel of Saraca asoca (Roxb.) De Wilde hydroalcoholic extract containing eucalyptus oil and peppermint oil as penetration enhancer

In the present research investigation, various concentrations of hydro-alcoholic extract of Saraca asoca (Roxb.) De Wilde (family: Caesalpinaceae) dried bark and carbopol polymer at different temperature ranges were optimized for the preparation of gel formulation. Natural penetration enhancers, v.i.z., eucalyptus oil and peppermint oil were incorporated separately in the extract based gel formulations to study the rate of drug permeation across egg membrane, using franz diffusion cell. In vitro anti-arthritis potential of the formulations was also studied using inhibition of albumin denaturation, antiproteinase activity and membrane stabilization method. As per the results of current study, it is established that S. asoca dried bark hydroalcoholic extract based gel prepared using peppermint oil as penetration enhancer exhibited good permeation rate of 8.48% at the end of 3 h. The percentage inhibition of proteins by antiproteinase method at concentration of 50 µg/ml was 50.01±1.00% which was close to 53.92±0.99% as shown by the standard drug, Diclofenac. Also, the percent protein inhibition determined using membrane stabilization method was found to be 49.70±1.00%, however, it was 63.32±0.94% for the standard drug, Diclofenac. Hence, it is concluded that peppermint oil may act as a good candidate for the preparation of potent anti-rheumatic gel preparations.

Stereolithography (SLA) 3D Printing Technology in Microneedles

Many of the drugs show enzymatic degradation in gastrointestinal tract (GIT) or they show difficulty in permeation. In these cases, microneedles (MN) based transdermal drug delivery system offers attractive alternative to conventional needle-based and oral drug delivery systems. Microneedle drug delivery system consists of an arrangement of micrometric arrays which can be formulated with the use of different polymers and technologies. This present review is related to manufacturing of biocompatible microneedles” formulated with an aid of stereolithography (SLA) - a 3D printing technique in which microneedle patches of different shapes are constructed in the form of layers. The MN patches could be coated using inkjet printing. An SLA printer could be employed to print pyramid needle-based arrays. X-ray computer micro tomography (CT) and scanning electronic microscopy (SEM) could be used to assess the standard of the formed microneedles and subsequent coatings. In vitro studies using Franz diffusion cells could be done further to analyze drug permeation rate and calculation of flux. Microneedles could be constructed by using a 3D printing stereolithographic technology, and combining it with a highly appropriate coating method like inkjet printing, which can lead to a high-paced drug delivery microneedle systems via skin.

PHARMACEUTICAL WORLD OF PERMEATION ENHANCERS

The drugs with poor solubility results in delayed absorption which consequently affects the bioavailability. There are many drugs which are having good therapeutic value but not used commercially because of this reason. The permeation enhancers are therefore being utilized to counter this problem. There are many such synthetic and natural materials which have the ability to enhance the drug permeation rate. The essential oils, alcohols, terpenes, azoles and many other chemical derivatives have the capability to be used for permeation enhancer. The present review work suggested the role of permeation enhancer in the pharmaceutical world.

EFFECT OF POLYMERIC BLEND ON EX-VIVO PERMEATION STUDIES OF ACECLOFENAC LOADED FILM FORMING GEL

Objective: To date, film-forming systems have been intensively investigated for transdermal drug delivery. Film-forming systems offers various advantages compared over conventional transdermal drug delivery systems. The objective of the present study was to study the effect of polymeric blend on ex-vivo permeation studies of topical film-forming gel of aceclofenac.&#x0D; Methods: Film-forming gels were prepared by using Hydroxypropyl methylcellulose and Eudragit polymeric blend in varied concentrations, polyethylene glycol 400 as plasticizer, ethanol as solvent and tween 80 as a penetration enhancer. The prepared film-forming gels were evaluated and the influence of the concentration and ratio of polymeric blends used plasticizer and ethanol were investigated.&#x0D; Results: All the prepared film-forming gels showed satisfactory properties regarding homogeneity, compatibility, viscosity and pH value. Variation in the concentration of polymers showed a variable effect on drug permeation rate from film-forming gels. Almost, all formulations permeated up to 80% of drug in 12 h and formulation F1 showed a maximum release about 97.54 % in 12 h.&#x0D; Conclusion: Film-forming gels of aceclofenac with sustained-release profile were successfully developed and may provide a promising effective formulation which may improve patient compliance.

Jojoba oil-based microemulsion for transdermal drug delivery.

Background and purpose:Microemulsions are gaining an increased interest in transdermal drug delivery. Microemulsions are stable, easy to prepare, and provide high solubilizing capacity for various drugs. The aim of this work was to prepare microemulsions from jojoba oil for transdermal delivery of ketorolac and lidocaine HCl with improved permeation.Experimental approach:Microemulsions based on jojoba oil as the oil phase were formulated for transdermal delivery of lidocaine HCl and ketorolac. Brij 97 was selected as surfactant and hexanol as cosurfactant. Pseudoternary phase diagrams were constructed. Selected microemulsion formulations were characterized for their physical properties and in vitro drug permeation.Findings/Results:Water-in-oil microemulsions were obtained with droplet sizes not more than 220 nm. The viscosity of the microemulsions was linked to the viscosity of the surfactant used. Improved drug permeation rates were observed for both model drugs. The significant increase in permeation rate in presence of hexanol was due to its impact on skin integrity as indicated by the histopathological study. Drug permeation enhancements were caused by the surfactant, the cosurfactant used, jojoba oil itself, and the microemulsion formulation. Higher surfactant content showed lower lag times and better flux.Conclusion and implications:Jojoba oil microemulsions are considered promising vehicles for transdermal delivery of ketorolac and lidocaine HCl with improved drug permeation. Jojoba oil-based microemulsion would present a safe and effective means for delivering drugs through the skin.

Polymeric Precipitation Inhibitor Based Supersaturable Self-microemulsifying Drug Delivery System of Canagliflozin: Optimization and Evaluation.

The present investigation attempts to optimize Supersaturable lipid based formulation (SS SMEDDS) of Biopharmaceutical Classification System (BCS) class IV drug canagliflozin (CFZ) and evaluating the oral bioavailability of the formulation. Preliminary screening revealed Poloxamer 188 to most effectively inhibit precipitation of CFZ after dispersion during in vitro supersaturation studies. Box Behnken Design was employed for designing different formulations, and various statistical analyses were done to select an appropriate mathematical model. The optimized formulation (OSS 1) was evaluated for in vitro drug release and ex vivo permeation studies to evaluate drug release and permeation rate. Pharmacokinetic studies have been carried out according to standard methodologies. The optimized formulation (OSS 1) containing 781.1 mg SS SMEDDS and 2.24% w/w Poloxamer 188 was developed at a temperature of 60°C, which revealed nano-globule size with negligible aggregation. Isothermal titration calorimetry revealed the thermodynamic state of formed microemulsion with negative ΔG. The optimized formulation was observed to possess physical stability under different stress conditions and acceptable drug content. In vitro dissolution of optimized SS SMEDDS revealed a higher dissolution rate of CFZ as compared to native forms of CFZ. The permeability of CFZ from optimized SS SMEDDS across various excised segments of rat intestine was observed to be multifold higher as manifested by 2.05-fold higher Cmax and 5.64- fold higher AUC0-36h following oral administration to Wistar rats. The results could be attributed to substantial lymphatic uptake and P-glycoprotein substrate affinity of CFZ in SS SMEDDS investigated through chylomicron and P-glycoprotein inhibition approach, respectively.

Efficient Prediction of InVitro Piroxicam Release and Diffusion From Topical Films Based on Biopolymers Using Deep Learning Models and Generative Adversarial Networks.

The purpose of this study was to simultaneously predict the drug release and skin permeation of Piroxicam (PX) topical films based on Chitosan (CTS), Xanthan gum (XG) and its Carboxymethyl derivatives (CMXs) as matrix systems. These films were prepared by the solvent casting method, using Tween 80 (T80) as a permeation enhancer. All of the prepared films were assessed for their physicochemical parameters, their invitro drug release and exvivo skin permeation studies. Moreover, deep learning models and machine learning models were applied to predict the drug release and permeation rates. The results indicated that all of the films exhibited good consistency and physicochemical properties. Furthermore, it was noticed that when T80 was used in the optimal formulation (F8) based on CTS-CMX3, a satisfactory drug release pattern was found where 99.97% of PX was released and an amount of 1.18mg/cm2 was permeated after 48h. Moreover, Generative Adversarial Network (GAN) efficiently enhanced the performance of deep learning models and DNN was chosen as the best predictive approach with MSE values equal to 0.00098 and 0.00182 for the drug release and permeation kinetics, respectively. DNN precisely predicted PX dissolution profiles with f2 values equal to 99.99 for all the formulations.

Hydrogel eye drops as a non-invasive drug carrier for topical enhanced Adalimumab permeation and highly efficient uveitis treatment

Uveitis is one of the most popular blind-causing eye diseases worldwide. Adalimumab (ADA) is used for the uveitis treatment through systemic or intravitreal injection at the expense of systemic side effects and increased medical risks. Although eye drops, a non-invasive topical treatment, could be a potential strategy to reduce side effects, it remains challenging to apply due to limited bioavailability mainly linked to poor retention time and permeation capacity for eye biological barriers. Here, we reported hydrogel eye drops composed of low-deacetylated chitosan and β-glycerophosphate as an ADA carrier and tested its toxicity, tolerability, intraocular permeability, and efficacy of non-invasive treatment for uveitis. It’s found the ADA-loaded hydrogel eye drops were more efficient than free ADA both in permeation rate and clinical efficacy for uveitis, Overall, this study provides a friendly non-invasive strategy to improve drug permeation rate and uveitis treatment efficacy, which may be valuable to clinically ophthalmic medication.

Functionally Tailored Electro-Sensitive Poly(Acrylamide)-g-Pectin Copolymer Hydrogel for Transdermal Drug Delivery Application: Synthesis, Characterization, In-vitro and Ex-vivo Evaluation

Background and Objectives: To develop electro-sensitive transdermal drug delivery systems (ETDDS) using polyacrylamide-grafted-pectin (PAAm-g-PCT) copolymer hydrogel for rivastigmine delivery. Methods: Free radical polymerization and alkaline hydrolysis technique was employed to synthesize PAAm-g-PCT copolymer hydrogel. The PAAm-g-PCT copolymeric hydrogel was used as a reservoir and cross-linked blend films of PCT and poly(vinyl alcohol) as rate-controlling membranes (RCMs) to prepare ETDDS. Results: The pH of the hydrogel reservoir was found to be in the range of 6.81 to 6.93 and drug content was 89.05 to 96.29%. The thickness of RCMs was in the range of 51 to 99 μ and RCMs showed permeability behavior against water vapors. There was a reduction in the water vapor transmission rate as the glutaraldehyde (GA) concentration was increased. The drug permeation rate from the ETDDS was enhanced under the influence of electric stimulus against the absence of an electric stimulus. The increase in flux by 1.5 fold was recorded with applied electric stimulus. The reduction in drug permeability observed when the concentration of GA was increased. Whereas, the permeability of the drug was augmented as an electric current was changed from 2 to 8 mA. The pulsatile drug release under “on– off” cycle of electric stimulus witnessed a faster drug release under ‘on’ condition and it was slow under ‘off’ condition. The alteration in skin composition after electrical stimulation was confirmed through histopathology studies. Conclusion: The PAAm-g-PCT copolymer hydrogel is a useful carrier for transdermal drug delivery activated by an electric signal to provide on-demand release of rivastigmine.

Formulation Designing Factors for Development of Repaglinide Transdermal Therapeutic System

Repaglinide, a blood-glucose-lowering drug, has a shorter half-life (~1 hour), low oral bioavailability (LOB) (~56 %) due to the first-pass metabolism, and required frequent dosing (Three to four times daily) to control blood glucose level. Repaglinide transdermal therapeutic system (TTS) was prepared to provide continuous drug delivery for a prolonged time. Designing factors for development are selection and optimization of product ingredients, optimization of drug load, types of TTS, matrix thickness, and optimization of drug delivery. During development, repaglinide TTS were evaluated for physicochemical characteristics and ex-vivo skin flux at different stages. Based on the pre-formulation study data, Durotak 87-2516® was selected as a pressure-sensitive adhesive. Different formulations of a drug in adhesive matrix and reservoir type repaglinide TTS were evaluated for ex-vivo skin permeation (flux) study. The skin flux results show that sandwiched reservoir type repaglinide TTS can provide average cumulative drug permeation and flux rate of 379.75 ± 47.89 μg/cm2 and 4.62 ± 1.00 μg/cm2/hr respectively for sustain drug delivery over the time of 72 hours. Developed sandwiched reservoir type repaglinide TTS has the potential to sustain delivery of drug for 72 hours, which reduce frequent dosing and thereby improve patient compliance.