Development of monolithic matrix type transdermal patches containing cinnarizine: Physical characterization and permeation studies

To overcome the problems associated with bioavailability and systemic side effects of the drug by oral administration, monolithic matrix type transdermal patches containing cinnarizine (CNZ) were developed. For this purpose, films based on hydroxypropyl methylcellulose and polyvinylpyrrolidone as matrix-forming polymers were designed. Physical characteristics of transdermal films and drug-excipient compatibility were investigated. Factors affecting in vitro drug release and ex vivo skin penetration and permeation of the drug were studied. It was confirmed that films displayed sufficient flexibility and mechanical strength for application onto the skin for a long time period. Ex vivo penetration experiments gave satisfactory results for transdermal drug delivery through rat skin. The parameters determining good skin penetration were also evaluated. The highest drug permeation rate was obtained with incorporation of Transcutol® (0.102 mg/cm2/h) into the base CNZ formulation, followed by propylene glycol (0.063 mg/cm2/h), menthol (0.045 mg/cm2/h), and glycerin (0.021 mg/cm2/h) as penetration enhancers (p < 0.05). As a result, the developed transdermal patches of CNZ may introduce an alternative treatment for various conditions and diseases such as idiopathic urticarial vasculitis, Ménière's disease, motion sickness, nausea, and vertigo. Thus, the risk of systemic side effects caused by the drug can be reduced or eliminated

Retrospective Analysis of Efficacy and Safety of Three High-dose Opioids in the Treatment of Cancer Pain / 中国药师

Objective: To retrospectively analyze the efficacy and safety of three high-dose opioids in the treatment of cancer pain in our hospital.Methods: The medical records of 73 patients with severe cancer pain were collected, and according to the taken drugs, they were divided into group A (sustained-release morphine tablets, 25 ones), group B (sustained-release oxycodone tablets, 36 ones) and group C (transdermal fentanyl, 12 ones).Evaluation of patients with average of pain NRS,breakthough pain NRS,dosage of opioids,quality of life on admission and in 24h after the 4 weeks treatment;In addition,the other analgesic medications,auxiliary medicines,and adverse drug reations were recorded at the same time.Results: The NRS was significantly lowed in the three groups after the 4-week treatment (P＜0.01), and that in group B was lowest with notable difference when compared with that in group A (P＜0.05).The number of breakthrough pain also significantly decreased in the three groups after the treatment (P＜0.01), and there was no significant difference among them (P＞0.05).The doses of opioids analgesics after the 4-week treatment were significantly higher than those on admission (P＜0.01), and the doses in group B were slightly lower than those in the other two groups, while there was no significant difference among them (P＞0.05).The quality of life in the three groups was improved significantly after the treatment (P＜0.01), and no significant difference was shown among them (P＞0.05).The other pain medications and auxiliary medicines used in the three groups were similar (P＞0.05).The incidence of adverse reactions in the three groups had no significant difference (P＞0.05).Conclusion: The standardization of the three high-dose opioids analgesics can control pain effectively and improve the quality of life, which is worthy of clinical promotion.In addition, oxycodone shows the best analgesic effect, whiel fentanyl transdermal patches have the lowest incidence of adverse reactions.

Liquid crystalline systems containing Vitamin E TPGS for the controlled transdermal nicotine delivery

ABSTRACT Transdermal nicotine patches have been used in smoking cessation therapy, suggested for the treatment of skin disorders with eosinophilic infiltration and have been found to improve attention performance in patients with Alzheimer's disease and age-associated memory impairment. However, skin irritation with extended patch use is still a problem. The aim of this work was to develop a simple to prepare liquid crystalline system containing vitamin E TPGS that would be able to control nicotine delivery and reduce irritation and sensitization problems. The liquid crystalline phases were macroscopically characterized by visual analysis and examined microscopically under a polarized light microscope. Topical and transdermal delivery of nicotine were investigated in vitro using porcine ear skin mounted on a Franz diffusion cell. Nicotine skin permeation from the developed cubic phase followed zero-order kinetics (r = 0.993) and was significantly enhanced after 12 h when compared to the control formulation (nicotine solution) (p < 0.05) (138.86 ± 20.44 and 64.91 ± 4.06 μg/cm2, respectively). Cubic phase was also able to target viable skin layers in comparison to control solution (8.18 ± 1.89 and 2.63 ± 2.51 μg/cm2, respectively). Further studies to evaluate skin sensitization and irritation are now necessary.

RESUMO Adesivos transdérmicos de nicotina são utilizados para cessação de fumar, tratamento de problemas de pele com infiltração de eosinófilos e para melhorar a atenção em pacientes com doença de Alzheimer e enfraquecimento da memória associada à idade. No entanto, a irritação da pele com o uso prolongado dos adesivos ainda é um problema. O objetivo deste trabalho foi desenvolver sistema líquido cristalino (SLC) de preparo simples contendo vitamina E TPGS capaz de controlar a liberação de nicotina e reduzir os problemas de irritação cutânea. Os SLCs foram caracterizados por análise visual e microscopia de luz polarizada. As administrações tópica e transdérmica de nicotina foram investigadas in vitro utilizando pele de orelha de porco em célula de difusão de Franz. A permeação da nicotina veiculada pela fase cúbica desenvolvida seguiu cinética de ordem zero (r = 0,993) e foi significativamente maior do que o controle (solução de nicotina) após 12 h (p < 0,05) (138,86 ± 20,44 e 64,91 ± 4,06 µg/cm2, respectivamente). A fase cúbica também promoveu aumento da penetração de nicotina nas camadas viáveis da pele quando comparado ao controle (8,18 ± 1,89 e 2,63 ± 2,51 µg/cm2, respectivamente). Estudos futuros para avaliar a sensibilização e irritação da pele são necessários.

Preparation, in vitro Characterization of Transdermal Patch Containing Atenolol and Hydrochlorothiazide: A Combinational Approach.

Background: In the present days, the prevalence of hypertension is potentially increasing. To overcome the effects of this disease, a complex therapeutic regimen is often introduced, but the patient compliance is always questionable. Methodology: To improve patient compliance, a novel approach has to be implemented. Hence, the present study was designed to develop a transdermal patch containing Atenolol and hydrochlorothiazide in combination using blends of different polymeric combinations such as hydroxypropyl methyl cellulose, sodium alginate, and polyethylene glycol. The patches were subjected to physicochemical tests and in-vitro drug release study. Results: Good results were obtained in all the evaluated parameters. The drug release of all formulation followed zero order kinetics. The medicated films also went through primary skin irritation test and the results showed that the films were non-irritant. Conclusion: The developed transdermal delivery system containing Atenolol & hydrochlorothiazide might be a milestone in the combinational therapy of hypertension.

Formulation and evaluation of transdermal drug-delivery system of isosorbide dinitrate / Formulação e avaliação de sistema transdérmico droga-entrega de dinitrato de isossorbida

The purpose of this study was to develop a reservoir-type transdermal delivery system for isosorbide dinitrate (ISDN). The developed patch consisted of five layers from bottom to top, namely, a temporary liner, an adhesive layer, a rate-controlling membrane, a reservoir and a backing. The effects of chemical penetration enhancers, reservoir materials and rate-controlling membranes on the release behaviour of ISDN from the transdermal patch were studied, and the in vitro release of ISDN from the developed patch was studied and compared with the commercially available ISDN patch. The results showed that there was no significant difference in permeation rates between the developed reservoir-type patch and the commercially available ISDN patch (p> 0.05). Moreover, the cumulative release ratio of the commercially available ISDN patch in 48 h was up to 89.8%, whereas the developed patch was only 34.9%, which meant the sustained release time of the developed patch was much longer than the commercially available ISDN patch, and would promote the satisfaction of the patient...

O objetivo do presente estudo foi desenvolver um sistema de liberação transdérmico do tipo reservatório para o dinitrato de isossorbida (ISDN, abrevitura em Inglês). A formulação transdérmica desenvolvida constou de cinco camadas de baixo para cima, ou seja, um revestimento temporário, uma camada adesiva, uma membrana controladora da taxa de liberação, um reservatório e um reforço. Estudaram-se os efeitos dos potenciadores de penetração química, materiais do reservatório e membranas de controle da taxa de liberação no comportamento da formulação transdérmica de dinitrato de isossorbida. A liberação in vitro da formulação transdérmica de dinitrato de isossorbida desenvolvida foi estudada em comparação com a formulação de dinitrato de isossorbida disponível comercialmente. Os resultados mostraram que não existem diferenças significativa nas taxas de permeação entre o tipo de reservatório desenvolvido e o de dinitrato de isossorbida desenvolvido comercialmente (p>0,05). Ademais, a taxa de liberação cumulativa da formulação de dinitrato de isossorbida disponível comercialmente em 48 horas foi de até 89,8% e a da formulação desenvolvida, de apenas de 34,9%, o que provou que a liberação sustentada da formulação desenvolvida foi muito maior do que a de dinitrato de isossorbida desenvolvida comercialmente, o que promoveria a satisfação do paciente...

Effect of different penetration enhancers on percutaneous absorption of active components groups in Shaofu Zhuyu Transdermal Patches / 中草药

Objective: To study the effect of different penetration enhancers on the percutaneous absorption of nine active components in Shaofu Zhuyu Transdermal Patches (SZTP) across skin of mice and optimize the proper penetration enhancers in order to provide the scientific basis for SZTP research, clinical medication, and reform of the traditional forms. Methods: Using improved Franz diffusion cells and taking isolated rat abdomen skins as transdermal barrier, the concentration of these components was determined by UPLC-MS/MS, then the total factor scores of the concentrations at different time were calculated using PCA and employed instead of the concentration to compute the cumulative amounts and steady fluxes. Results: The results showed that compared to the control group, the steady fluxes of the other groups increased significantly, and furthermore, 2.5% azone with 2.5% propylene glycol manifested the best effect. The nine components could penetrate through skin well under the action of penetration enhancers. Conclusion: Azone and propylene glycol could significantly promote the percutaneous penetration effect of the nine active components in SZTP, and it could provide a scientific basis for the preparation research of SZTP.

Clinical research of transdermal estrogen patches in hormone therapy of menopausal women / 中国药学杂志

OBJECTIVE: To investigate the efficacy, safety and patient compliance of transdermal estrogen patches(17-β estradiol, 1.5 mg per patch) in the hormone therapy in menopausal women. METHODS: Thirty-five naturally menopausal women with serum levels of FSH >40 u · L-1 and E2 < 30 pg · mL-1 were chosen. Transdermal estrogen patches were continuously used once a week for 24 weeks. On the same day of using the forth patches every month, the patients began taking 10 mg dydrogesterone per day for 10 d. Menopausal complaints were evaluated, and the serum FSH and E2 levels were determined before and after the hormone therapy. The safety index and the compliance of patients were observed. RESULTS: Kupperman index were decreased significantly and menopausal complaints were relieved notablely; serum E2 levels increased after therapy. Before and after treatment, liver and kidney functions, blood glucose and blood coagulation were within the normal range. CONCLUSION: Transdermal estrogen patches (17-β estradiol, 1.5 mg per patch) is effective and safe for relieving menopausal symptoms at least in a short term.

Formulation and evaluation of transdermal patches and to study permeation enhancement effect of eugenol.

Since oral bioavailability of Propranolol Hydrochloride is poor due to high first pass metabolism different matrix- type transdermal patches incorporating Propranolol Hydrochloride were formulated with an objective to study the effect of polymers on transdermal release of the drugs. The polymers selected for sustaining the release of drug were polyvinylpyrrolidone, Hydroxypropylmethycellulose (HPMC) and Ethyl cellulose (EC). The patches were formulated using combination of polymers and propylene glycol as plasticizer. The physicochemical evaluation of the polymer matrices was performed for suitability. In vitro permeation studies were performed using rat abdominal skin as the permeating membrane in Franz diffusion cell. The result indicated that maximum release was obtained at 2% solution of EC. Optimized batch was evaluated for permeation enhancement through rat skin using natural permeation enhancer Eugenol and it was concluded that permeation enhancement through Eugenol was comparable to the commercially available permeation enhancer Dimethyl sulfoxide 1% (DMSO). All the films were found to be stable at 37ºC and 45ºC with respect to their physical parameters and drug content.

Fabrication and in- vitro permeation studies of indomethacin-ficus carica fruit mucilage patches.

The main objective of the present study was to develop matrix-moderated transdermal systems of Indomethacin using various proportions of Ficus carica fruit mucilage. Physical evaluation was performed such as moisture content, moisture uptake, tensile strength, flatness and folding endurance. In-vitro permeation studies were performed in a Keshary-Chien diffusion cell. The matrix-type transdermal systems were prepared using Indomethacin with Ficus carica fruit mucilage by the solvent evaporation technique. The interactions between Indomethacin and Ficus carica fruit mucilage were performed. The transdermal patches were subjected to various physicochemical parameters viz., mechanical properties, permeation studies and skin irritation studies. The prepared patches possessed satisfactory pre-formulary and formulary characteristics. In vitro permeation studies were performed using a Keshary-Chien diffusion cell across hairless Albino rat skin. The non-ionic surfactants Span 80, Glycerin, Propylene glycol in the formulation played a role as permeability enhancer. The patches were seemingly free of potentially hazardous skin irritation. The experimental results shows that the release of drug from the patch delayed in controlled manner as the proportion of Ficus carica increased. It was concluded that Indomethacin can be developed as a transdermal patches with Ficus carica fruit mucilage.

Efficacy Observation of Fentanyl Transdermal Patches in the Treatment of Cancer Pain / 中国药房

OBJECTIVE:To evaluate the analgesic effects and ADR of fentanyl transdermal patches in different therapies. METHODS:189 patients with cancer pain were randomized into three groups:routine dose fentanyl transdermal patches group(group A) ;routine dose fentanyl transdermal patches +12 h controlled-release morphines(Ms) group(group B) ;twice routine dose fentanyl transdermal patches+12 h controlled-release Ms group(group C) . The curative effects of treatment for 6 days in3 groups were compared by VAS method. RESULTS:In group A,B and C,significant differences were noted in curative efficacy(P0.05) . CONCLUSION:The therapy of group C shows better analgesic effect,safety and clinical value than the other two groups.