Use of transethosomes for enhancing the transdermal delivery of olmesartan medoxomil: in vitro, ex vivo, and in vivo evaluation (original) (raw)
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International Journal of Nanomedicine
Introduction and aim: Olmesartan medoxomil (OLM) is an antihypertensive drug with low oral bioavailability due to extensive first-pass metabolism. This study aimed to prepare transetho somes (TEs) for enhancing the transdermal delivery of OLM to avoid its oral problems. Methods: TE formulae were prepared utilizing 5 1 .3 1 full factorial design using various surfactants (SAAs) and different phospholipid-to-SAA ratios. The formulae were characterized regarding their entrapment efficiency percentage (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and the amount of drug released after 6 hours (Q6h). Design Expert ® software was employed to select the optimum formula. Results: The optimum formula (TE14) had an EE% of 58.50%±1.30%, PS of 222.60±2.50 nm, PDI of 0.11±0.06, ZP of-20.80±0.30 mV, and Q6h of 67.40%±0.20%. In addition, TE14 was compared to transferosomes (TFs) in terms of elasticity and was found to show higher deformability index. Further, evaluation of ex vivo permeation using both rat and shed snake skin showed higher permeability of TE14 compared to TFs and OLM suspension. Confocal laser scanning microscopy confirmed the capability of the fluoro-labeled TE14 to penetrate deep within the skin, while the histopathological study confirmed its safety. TE14 successfully maintained normal blood pressure values of rats up to 24 hours. Moreover, TE14 showed superiority in dermatokinetic study when compared with drug suspension. Conclusion: Taken together, the obtained results confirmed the potential of employing TEs as a successful carrier for the transdermal delivery of OLM.
International Journal of Nanomedicine, 2019
Introduction and aim: Olmesartan medoxomil (OLM) is an antihypertensive drug with low oral bioavailability due to extensive first-pass metabolism. This study aimed to prepare transetho somes (TEs) for enhancing the transdermal delivery of OLM to avoid its oral problems. Methods: TE formulae were prepared utilizing 5 1 .3 1 full factorial design using various surfactants (SAAs) and different phospholipid-to-SAA ratios. The formulae were characterized regarding their entrapment efficiency percentage (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and the amount of drug released after 6 hours (Q6h). Design Expert ® software was employed to select the optimum formula. Results: The optimum formula (TE14) had an EE% of 58.50%±1.30%, PS of 222.60±2.50 nm, PDI of 0.11±0.06, ZP of-20.80±0.30 mV, and Q6h of 67.40%±0.20%. In addition, TE14 was compared to transferosomes (TFs) in terms of elasticity and was found to show higher deformability index. Further, evaluation of ex vivo permeation using both rat and shed snake skin showed higher permeability of TE14 compared to TFs and OLM suspension. Confocal laser scanning microscopy confirmed the capability of the fluoro-labeled TE14 to penetrate deep within the skin, while the histopathological study confirmed its safety. TE14 successfully maintained normal blood pressure values of rats up to 24 hours. Moreover, TE14 showed superiority in dermatokinetic study when compared with drug suspension. Conclusion: Taken together, the obtained results confirmed the potential of employing TEs as a successful carrier for the transdermal delivery of OLM.
International Journal of Nanomedicine
Introduction: The intention of this work was to load olmesartan medoxomil (OLM), a sparsely water soluble antihypertensive bioactive with low oral bioavailability (26%), into PEGylated bilosomes (PBs) for augmenting its transdermal delivery. PBs contain PEGylated single chain edge activator besides the components of traditional bilosomes (Span 60, cholesterol and bile salts). The PEG gives further resilience to vesicle membrane and is speculated to augment both permeability and bioavailability of OLM. Methods: A 2 4 factorial experiment was constructed to inspect the impact of diverse variables on vesicles' features and sort out the optimal formula adopting Design Expert ® software utilizing thin film hydration technique. Vesicles' evaluation was done by finding out entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP) and amount of drug released after 6 hrs (Q6h). The optimal formula was selected and characterized for further investigations. Results: The optimal formula (PB15) showed spherical vesicles with EE% of 72.49±0.38%, PS of 559.30±10.70 nm, PDI of 0.57±0.15, ZP of −38.35±0.65 mV and Q6h of 59.60±0.24%. PB15 showed higher deformability index (28.39±5.71 g) compared to traditional bilosomes (5.88±0.90 g) and transethosomes (14.94±0.63 g). Further, PB15 showed superior skin permeation from rat's skin relative to the drug suspension. Moreover, confocal laser scanning microscopy examination revealed efficient penetration of the fluoro-labeled PB15 through skin. Histopathological study ensured the safety of PB15. In addition, in-vivo skin deposition studies showed higher OLM deposition in rat's skin from PB15 compared to transethosomes and OLM suspension. Furthermore, pharmacodynamic and pharmacokinetic studies performed using male Wistar rats and male Albino rabbits, respectively, showed the superiority of PB15 over oral tablets. PB15 was found to have significantly higher AUC 0-48 and AUC 0-∞ relative to the oral tablets. As well, the relative bioavailability of PB15 was found to be 235.04%. Conclusion: Overall, the obtained results confirmed the creditable effect of PB15 for transdermal delivery.
AN OVERVIEW: RECENT DEVELOPMENT IN TRANSDERMAL DRUG DELIVERY Review Article
International Journal of Pharmacy and Pharmaceutical Sciences, 2022
The transdermal drug delivery system is an alternative method of administration of drugs. Most of the drugs are delivered by conventional oral, topical, intravenous, and intramuscular methods and are is of limited efficiency. However, now the clinical use of transdermal delivery is limited because of stratum cornea of the skin act as an effective barrier that limits the permeation of drugs through the skin. To overcome this disadvantage, there are Recent developments in transdermal drug delivery, such as the usage of nanoparticles i.e., liposomes, niosomes, transferosomes, ethosomes, nanoemulsion, virosomes, phytosomes, dendrimers, proniosomes, microneedles, and separable microneedles. This nanoparticulate transdermal drug delivery exhibits great potential to ensure drug permeation through the skin. They are very tiny carriers to detect by the immune system and further, they can be delivering the drug to the targeted site and also have the ability to deliver both hydrophilic and hydrophobic drugs by reducing the complexity. Nanoparticles are made of different materials and they're very different in structure and chemical properties are discussed in this review article.
Review on Transdermal Drug Delivery Systems
Journal of Pharmaceutics and Drug Development, 2014
During the past decades, intensive studies have focused on the technologies in drug delivery, and with the rapid developments and explorations in technologies, traditional drug delivery means are being replaced by the more effective and advanced ones. The creation of transdermal drug delivery system (TDDS) has been one of the most sophisticated and innovative approaches of drug deliveries. The transdermal drug delivery system has attracted considerale attention because of its many potential advantages, including better patient compliance, avoidance of gastrointestinal disturbances, hepatic first-pass metabolism and sustained delivery of drugs to provide steady plasma profiles, particularly for drugs with short half-lives, reduction in systemic side effects and enhanced therapeutic efficacy [1-6]. Recently, transdermal drug delivery system (TDDS) has become a more and more important approach to administering drugs. Based on its advantages, which are not achievable by other modes of administration, many researchers are dedicated to the study of it, and have made great progress. Although the skin offers a painless interface for systemic drug delivery, it also presents limitations which are mainly caused by the stratum corneum. In this work, we state the increasingly impact of TDDS, discuss the limitations of it, and last but not least, we highlight the methods for overcoming these limitations by using permeation enhancers, microneedles, iontophoresis. Despite these advantages, most of the transdermal candidates have low permeability. The drugs administered across skin should have the three constraining characteristics: appropriate partition coefficient, low molecular mass (<500Da), and small required dose (upto milligrams) [3]. The limitations of transdermal drug delivery are caused by skin which protects against and is impermeable to foreign molecules. The human skin is consisted of two main layers: the layer of epidermis and the layer of dermis. Stratum corneum is the epidermis's outermost layer that composed of stratified keratinocytes, multiple lipid bilayers of ceramidas, fatty acids, cholesterol and cholesterol esters. Stratum corneum provides an extremely effective physical barrier for the control of drug penetration [2,7-10]. Therefore, attempts to overcome this skin barrier is presently an important area of pharmaceutical and toxicological research. The techniques that weaken the barrier have included permeation enhancers [11-43], microneedles [44-68] and iontophoresis [69-84]. Chemical permeation enhancers In the last 50 years, a large number of chemical permeation enhancers (CPEs) which are defined as substances that interact with the major constituents of skin barrier, stratum corneum, to promote penetration of drugs into skin. The ideal enhancer should have the following conditions: 1. Non-pharmacological activities. 2. Nontoxic, non-allergenic, and non-irritating. 3. Rapid-acting with predictable and reproducible activity. 4. When removed from the skin surface, the penetrability of the skin should recover immediately. 5. Cosmetically acceptable with suitable skin feel [11]. The part of penetration enhancer in topical formulations has been becoming significantly and undoubtedly, and they would permit the delivery of broader classes of drugs through the stratum corneum in the future.
Transdermal Drug Delivery Systems - A Review
A sophisticated write-up which explains every aspect of drug delivery through transdermal route. Mostly focuses on its formulation based approaches with characterization and evaluations. Alongside, some basic information related to its invivo and pharmacokinetic studies also enclosed.
Innovations in Transdermal Drug Delivery: Formulations and Techniques
Recent Patents on Drug Delivery & …, 2007
The transdermal route of drug delivery has attracted researchers due to many biomedical advantages associated with it. However, excellent impervious nature of skin is the greatest challenge that has to be overcome for successfully delivering drug molecules to the systemic circulation by this route. Various formulation approaches used to systemically deliver drug molecules include use of prodrugs/lipophilic analogs, permeation enhancers, sub saturated systems and entrapment into vesicular systems. Further, the adhesive mixture, physical system of the delivery system and release liner influence drug release and its permeation across the skin. In addition, great strides in designing delivery systems for maximizing percutaneous drug permeation without comprising with ease of therapy cannot be neglected in improving functionality of transdermal drug delivery systems. This article deals with the innovations pertaining to formulation and techniques as described in recent patents.
Permeation enhancer strategies in transdermal drug delivery
Drug Delivery, 2014
Today, $74% of drugs are taken orally and are not found to be as effective as desired. To improve such characteristics, transdermal drug delivery was brought to existence. This delivery system is capable of transporting the drug or macromolecules painlessly through skin into the blood circulation at fixed rate. Topical administration of therapeutic agents offers many advantages over conventional oral and invasive techniques of drug delivery. Several important advantages of transdermal drug delivery are prevention from hepatic first pass metabolism, enhancement of therapeutic efficiency and maintenance of steady plasma level of the drug. Human skin surface, as a site of drug application for both local and systemic effects, is the most eligible candidate available. New controlled transdermal drug delivery systems (TDDS) technologies (electrically-based, structure-based and velocity-based) have been developed and commercialized for the transdermal delivery of troublesome drugs. This review article covers most of the new active transport technologies involved in enhancing the transdermal permeation via effective drug delivery system.
Transdermal Drug Delivery System is the system in which the delivery of the active ingredients of the drug occurs through the skin . Drug delivery through the skin to achieve a systemic effect of a drug is commonly known as transdermal drug delivery and differs from traditional topical drug delivery. Transdermal drug delivery systems (TDDS) are dosage forms involves drug transport to viable epidermal and or dermal tissues of the skin for local therapeutic effect while a very major fraction of drug is transported into the systemic blood circulation.This review article covers a brief outline of the trasdermal drug delivery system, advantages over conventional drug delivery system, Layers of the skin, various components of transdermal patch, penetration enhancers, and evaluation of transdermal system and applications of Transdermal patch.