ネオキシ^|^reg;テープ（経皮吸収型過活動膀胱治療剤）の開発

Transdermal drug delivery system has been in existence for a long time. In the past, the most commonly applied systems were topically applied creams and ointments for dermatological disorders. The occurrence of systemic side-effects with some of these formulations is indicative of absorption through the skin. A number of drugs have been applied to the skin for systemic treatment. In a broad sense, the term transdermal delivery system includes all topically administered drug formulations intended to deliver the active ingredient into the general circulation. Transdermal therapeutic systems have been designed to provide controlled continuous delivery of drugs via the skin to the systemic circulation. The relative impermeability of skin is well known, and this is associated with its functions as a dual protective barrier against invasion by micro-organisms and the prevention of the loss of physiologically essential substances such as water. Elucidation of factors that contribute to this impermeability has made the use of skin as a route for controlled systemic drug delivery possible. Basically, four systems are available that allow for effective absorption of drugs across the skin. The microsealed system is a partition-controlled delivery system that contains a drug reservoir with a saturated suspension of drug in a water-miscible solvent homogeneously dispersed in a silicone elastomer matrix. A second system is the matrix-diffusion controlled system. The third and most widely used system for transdermal drug delivery is the membrane-permeation controlled system. A fourth system, recently made available, is the gradient-charged system. Additionally, advanced transdermal carriers include systems such as iontophoretic and sonophoretic systems, thermosetting gels, prodrugs, and liposomes. Many drugs have been formulated in transdermal systems, and others are being examined for the feasibility of their delivery in this manner (e.g., nicotine antihistamines, beta-blockers, calcium channel blockers, non-steroidal anti-inflammatory drugs, contraceptives, anti-arrhythmic drugs, insulin, antivirals, hormones, alpha-interferon, and cancer chemotherapeutic agents). Research also continues on various chemical penetration enhancers that may allow delivery of therapeutic substances. For example, penetration enhancers such as Azone may allow delivery of larger-sized molecules such as proteins and polypeptides.

Compared with traditional oral and injection administration, the transdermal administration of traditional Chinese medicine has distinctive characteristics and advantages, which can avoid the “first pass effect” of the liver and the destruction of the gastrointestinal tract, maintain a stable blood concentration, and prolong drug action time. However, the basic theory and technology research in transdermal drug delivery are relatively limited at present, especially regarding research on new carriers of transdermal drug delivery and pharmacokinetic studies of the skin, which has become a bottleneck of transdermal drug delivery development. Triptolide is one of the main active components of Tripterygium wilfordii, which displays activities against mouse models of polycystic kidney disease and pancreatic cancer but its physical properties and severe toxicity limit its therapeutic potential. Due to the previously mentioned advantages of transdermal administration, in this study, we performed a detail analysis of the pharmacokinetics of a new transdermal triptolide delivery system. Triptolide nanoemulsion gels were prepared and served as new delivery systems, and the ex vivo characteristics were described. The metabolic characteristics of the different triptolide transdermal drug delivery formulations were investigated via skin–blood synchronous microdialysis combined with LC/MS. A multiscale modeling framework, molecular dynamics and finite element modeling were adopted to simulate the transport process of triptolide in the skin and to explore the pharmacokinetics and mathematical patterns. This study shows that the three−layer model can be used for transdermal drug delivery system drug diffusion research. Therefore, it is profitable for transdermal drug delivery system design and the optimization of the dosage form. Based on the drug concentration of the in vivo microdialysis measurement technology, the diffusion coefficient of drugs in the skin can be more accurately measured, and the numerical results can be verified. Therefore, the microdialysis technique combined with mathematical modeling provides a very good platform for the further study of transdermal delivery systems. This research will provide a new technology and method for the study of the pharmacokinetics of traditional Chinese medicine transdermal drug delivery. It has important theoretical and practical significance in clarifying the metabolic transformation of percutaneous drug absorption and screening for appropriate drugs and dosage forms of transdermal drug delivery.

Мета роботи. Узагальнити дані літературних джерел щодо переваг та недоліків, класифікації, особливостей технології трансдермальних терапевтичних систем.Матеріали і методи. У роботі використано методи інформаційного пошуку, аналізу даних літератури щодо трансдермальних систем та перспектив їх використання у медичній практиці.Результати й обговорення. Трансдермальні терапевтичні системи доставки лікарських речовин успішно розвиваються як альтернатива системному введенню ЛР та являють собою препарати, які наносяться на поверхню тіла і призначені для доставки певної дози активного фармацевтичного інгредієнта через шар шкіри безпосередньо в кров’яне русло або ж сприяють загоєнню травмованої ділянки тіла. Усі трансдермальні системи класифікують за трьома поколіннями розвитку. Залежно від методу введення лікарських речовин в систему, вони поділяються на три категорії: системи матричного, резервуарного та мікрорезервуарного типів.Висновки. Переваги таких лікарських засобів та позитивні рішення впровадження розробок трансдермальних терапевтичних систем у промислове виробництво активізували науково-дослідницьку діяльність у даному напрямку.

Polymeric membranes with skin-mimetic permeability properties appear as attractive models for use in the development of transdermal drug delivery systems. These membranes can be placed in contact with the transdermal system and simulate the skin barrier. In the current work, statistical experimental design was implemented for preparation of the optimized chitosan membrane to mimic human epidermis. For this purpose, an optimization process based on response surface methodology was carried out in order to determine the best combination of independent factors for membrane preparation. The independent factors analyzed were concentration of chitosan, concentration of cross-linking agent, and cross-linking time. The optimized membrane successfully simulated the cumulative amount of estradiol released per unit time for human epidermis. In addition, the optimized membrane was evaluated for the development of an estradiol delivery system. This in vitro technology may offer an alternative methodology for the development of transdermal delivery systems.

Transdermal drug delivery system constitutes one of the most important routes for new drug delivery system. Transdermal delivery of drugs offers several advantages over conventional delivery methods. Transdermal delivery, that traditionally uses a patch containing drug substance pressed onto the skin, is non-invasive, convenient and painless, and can avoid gastrointestinal toxicity (e.g. peptic ulcer disease) and the hepatic first pass metabolism. Transdermal delivery of drugs through the skin to the systemic circulation provides a convenient route of administration for a variety of clinical indications. In present study, attempt is made to prepare transdermal patches containing an anti- inflammatory drug such as oleanic acid along with various polymers for controlled release action. In present study, attempt was made to prepare Transdermal patches containing an anti-inflammatory drug such as oleanic acid along with various polymers for controlled release action. The Transdermal patch of oleanic acid was prepared successfully by solvent evaporation method. Transdermal patch of oleanic acid for Transdermal drug delivery was evaluated. Calibration curve was obtained; Transdermal film was prepared, overcome limitations regarding bioavailability of drug was done. Characterization was done by morphological study (SEM Analysis).

Transdermal drug delivery system used to transport the drug across the skin deep into systemic circulation. The main advantages of Transdermal drug delivery system improved patient compliance, sustained release, avoidance of gastric irritation, as well as elimination of pre-systemic first-pass effect. But most of therapeutic agents is limited due to thickness of stratum corneum, which act as a barrier for the delivery of various drug molecules and only few molecules are able to reach the action site. Microneedles are the new form of delivery system, which are used to increase the delivery of drug through this route and overcoming the number of problems related to conventional drug delivery system the main aim of this review to focus on new innovation in transdermal drug delivery systems. In the microneedle drug delivery system, the skin is temporarily broken, that creating micron size pathways that deliver the sufficient amount of drug directly into the stratum corneum from which the drug can directly go into the systemic circulation. In this review, we describe different type of microneedles can be solid, coated, dissolving and biodegradable microneedles and their method of fabrication. Microneedles can be manufactured in different forms like hollow, solid, and dissolving. Also describe materials used for fabrication, fabrication techniques, methodology of drug delivery such as Poke and patch, Coat and poke, Poke and release, Poke and flow and evaluation parameters.

Transdermal drug delivery is an attractive alternative to the oral and parenteral drug delivery. Drugs which are prone to first-pass metabolism can be delivered easily in small doses with sustained blood levels through this method. An update to available products along with a review of clinical trials and patents are discussed in this study. In this review, we have compiled 16 drugs, i.e. Buprenorphine, Clonidine, Estradiol, Fentanyl, Granisetron, Lidocaine, Methylphenidate, Nicotine, Nitroglycerin, Oxybutynin, Rivastigmine, Rotigotine, Scopolamine, Selegiline, Testosterone, Influenza virus vaccine (Microneedle) and covering about 22 marketed products on the transdermal system. We present instrumental information on them along with the compilation of current clinical trials on transdermal systems. We summarize the contents of patents granted in last 5 years under different pharmacological categories. This article serves, accordingly as a source of available information focused on transdermal drug delivery research.

Recent advances in drug delivery technologies utilizing a variety of carriers have resulted in a paradigm shift in the current approach to diagnosis and therapy. Mesoporous silica nanoparticles (MSNs) were developed in response to the need for materials with high thermal, chemical, and mechanical properties. The synthesis, ease of surface functionalization, tunable pore size, large surface area, and biocompatibility of MSNs make them useful in a variety of biomedical applications such as drug delivery, theranostics, and stem cell research. In addition, MSNs have a high capability of delivering actives ranging from small molecules such as drugs and amino acids to larger peptides, vaccines, and antibodies in general. Moreover, MSN-based transdermal delivery has sparked a lot of interest because of the increase in drug stability, permeation, and ease of functionalization. The functionalization of MSNs plays an important role in the efficient delivery of therapeutic agents in a highly controlled manner. This review introduced dermal and transdermal drug delivery systems, explained the anatomy of the skin, and summarized different barriers that affect the transdermal delivery of many therapeutic agents. In addition, the fundamentals of MSNs together with their physicochemical properties, synthesis approaches, raw materials used in their fabrication, and factors affecting their physicochemical properties will be covered. Moreover, the applications of MSNs in dermal and transdermal delivery, the biocompatibility of MSNs in terms of toxicity and safety, and biodistribution will be explained with the help of a detailed literature review. The review is covering the current and future perspectives of MSNs in the pharmaceutical field with therapeutic applications.

Transdermal delivery of peptide and protein drugs may be limited by the stratum corneum, which is a protective barrier against the entry of microorganisms and water. Many approaches have been utilized to promote peptide and protein drugs delivery across the stratum corneum, including chemical enhancer modification and physical disruption of barrier function. However, it has been difficult to achieve therapeutic levels of peptide and protein drugs via this route without any skin irritation. Recently, attention has been paid to the possibility of using microneedle arrays in delivering peptide and protein drugs into the skin. As a novel and minimally invasive approach, microneedle arrays are capable of creating superficial pathways across the skin for peptide and protein drugs to achieve enhanced transdermal drug delivery. This method combines the efficacy of conventional injection needles with the convenience of transdermal patches, while minimizing the disadvantages of these administration methods. Therefore, microneedle arrays are a very useful alternative method for delivering peptide and protein drugs from the skin into the systemic circulation without any serious damage to skin. In this review, recent challenges in the developments of microneedle arrays for the delivery of peptide and protein drugs are summarized. Then, future developments of microneedle arrays for the delivery of peptide and protein drugs are also discussed in order to improve their therapeutic efficacy and safety.

Transdermal drug delivery systems are preferred for both local and systemic effects. Administration of therapeutic agents with these drug delivery systems provides controlled and sustained release. Among these delivery systems, nanoparticles have a very common use. The use of polymers with different properties can determine the characteristics of nanoparticles such as size, surface charge, and drug release profile and can be modified for passage through the skin. Diffusion cells are the gold standard for skin permeation studies of drugs incorporated with topical or transdermal delivery systems, and Franz diffusion cells are the most ones. The evaluation of penetration of drugs into the skin is important for topical formulations where the expected effect is targeted to the superficial layers of the skin. Tape stripping and microscopic and spectroscopic methods can be used to evaluate skin penetration.

Due to the stratum corneum barrier, resveratrol is difficult to be absorbed transdermally, limiting its anti-aging and skin-brightening effects. Furthermore, there is a lack of systematic studies on the efficacy of resveratrol in human skin, especially in three-dimensional skin models and clinical trials. To overcome the low transdermal delivery issue, we encapsulated resveratrol into nanoliposomes using the high-pressure homogenization method to develop an efficient transdermal drug delivery system, and systematically evaluated its anti-aging and skin-brightening efficacy via cell line models, a three-dimensional skin model and human skin. The resveratrol nanoliposomes effectively improved the transdermal penetration and retention of resveratrol and enhanced cellular uptake. In addition, compared to free resveratrol, resveratrol nanoliposomes remarkably enhanced the skin-care effects by promoting the antioxidant capacity and collagen synthesis, inhibiting the secretion of matrix metalloproteinases, tyrosine activity and melanin synthesis. Notably, human clinical trials proved the anti-wrinkle and skin-brightening effectiveness of resveratrol nanoliposomes. Three levels of systematic studies indicated that resveratrol nanoliposomes could be a promising transdermal drug delivery system to enhance the anti-aging and skin-brightening effects of resveratrol.

Transdermal drug delivery systems in diabetes management: A review

Potential and problems of developing transdermal patches for veterinary applications

Transdermal drug delivery has been applied as a safe and efficient delivery system since 1981. TDDS recently accessible to dominate the problems of drug delivery over the oral route. Transdermal film is a therapeutic adhesive film which is used on the skin to deliver a particular amount of drug over the skin as well as systemic circulation. Development of an effective TDDS is dependent to physicochemical properties of drug, excipients and manufacturing possesses. For achieving systemic effect, many new carriers have been established such as Liposomes, Niosomes, Transfersomes, Cubosome and Ethosomes, an enormous request for pharmaceutical and cosmeceutical industry, it has capability to controlled the release of active ingredient, enhance consistency and bioavailability. In this review, we have summarized many physicochemical approaches for transdermal drug delivery system, containing classification of TDDS, enhancing the permeability of drug over the skin, marketed formulation and application of transdermal drug delivery system.

Transdermal drug delivery carried out a promising carrier in the transport of drugs to get direct access across the skin deep into the systemic circulation. Transdermal drug delivery have a number of advantages including improved patient compliance, sustained release, avoidance of gastric irritation, as well as elimination of pre-systemic first-pass effect. It gives attraction to many researchers due to various biomedical advantages. Due to the limitation of oral drug delivery system and the pain related with the use of needles in case of injections, drug delivery research has tremendously oriented towards the transdermal route. Delivery of drugs via transdermal route has proved to be the convenient route for various clinical implications. The objective of the present review is to focus on newly innovations in transdermal drug delivery systems which can create a platform for the research and development of pharmaceutical drug dosage form for efficient transdermal delivery. In this review, we tell about different types of microneedles are described and their methods of fabrication. Microneedles can be fabricated in different forms like hollow, solid, and dissolving. There are also hydrogel-forming microneedles. In relation to hydrogel-forming microneedles, special attention, these are innovative microneedles which does not contain drugs but imbibe interstitial fluid to form continuous conduits between dermal microcirculation and an attached patch-type reservoir. Regulatory authorities approved several microneedles for clinical uses are also examined. The last part of this review discusses concerns and challenges regarding microneedles use.