Penetration Enhancement Techniques Research Articles

Increasing Efficiency of Transdermal Drug Delivery Systems Using Some Novel Penetration Enhancement Techniques - A Critical Review

The transdermal route has drawn considerable attention and has emerged as a solid alternative to mimic the drawbacks of drugdelivery through the oral and parenteral routes. However, the effectiveness of TDDS is often limited by the skin's outermost layer, the stratumcorneum (SC), which acts as a barrier to drug diffusion. In addition, the drug molecule's molecular weight, hydrophilicity, and ionic nature canalso impact its transdermal delivery. Various methods have been developed to overcome these limitations to facilitate drug penetration acrossthe SC, including nano-carriers, wearable delivery systems, and combination-based approaches. The use of nano-carriers, such as dendrimers,liposomes, niosomes, and micro sponges, has shown promise in enhancing the efficacy of TDDS. Another emerging innovation for TDDS iswearable delivery systems, which offer non-invasive, convenient, and extended drug administration. Additionally, combination-based approaches,such as ultrasound and microneedle-based systems or ultrasound and electrical-based techniques, are also being investigated and are the centerof attraction in the research of TDDS approaches. This review summarizes a combination of all different novel penetration enhancementtechniques used to enhance the efficacy of transdermal drug delivery systems that were not precisely captured by other review articles. Most ofthe review articles emphasized these penetration enhancement techniques separately. However, a careful review of all the penetrationenhancement techniques in one article is missing. Thus, the purpose of this article is to comprehensively review and summarize the recentlyused penetration enhancement techniques along with the possible mechanism of action in a single article. Our primary aim is to collect relevantreviews and research articles by searching various databases to provide a comprehensive overview of the field. By providing a comprehensiveoverview of the available techniques, this review article will help students and researchers stay up-to-date with the latest developments in thefield of novel penetration enhancement techniques used to increase the efficiency of TDDS.

Development and Evaluation of a Meloxicam Topical Ointment for Localized Drug Delivery

The introduction of this research paper sheds light on the background and significance of employing topical drug delivery methods to enhance the localized effects of NSAIDs, such as meloxicam. The introductory section underscores the potential benefits of utilizing skin penetration enhancement techniques to augment the efficacy of the ointment. The materials and techniques section comprehensively outlines the constituents employed in the study, including meloxicam and excipients. Special attention is dedicated to ensuring the stability and compatibility of the formulation components, with thorough investigations into drug-excipient interactions. Following the formulation’s development, a meticulous characterization of the ointments is conducted, encompassing their physicochemical attributes and drug release profiles. Concurrently, in vitro skin permeation experiments elucidate meloxicam’s capability to permeate the skin and elicit its therapeutic effects. The resultant characterization data yield valuable insights into the physical characteristics of the ointments. In conclusion, this thesis study substantially advances our comprehension of meloxicam topical ointment formulation development and evaluation for localized drug delivery. The findings gleaned from this study provide invaluable insights into the feasibility and effectiveness of employing a meloxicam-infused ointment. Such an approach holds the promise of offering a compelling alternative to conventional systemic administration, mitigating systemic side effects, and concurrently maximizing the localized therapeutic advantages of meloxicam.

Transdermal Drug Delivery System

(TDDS), additionally called ‘ Transdermal patches,’ square measures dose form design to deliver a The human skin is readily accessible surface for drug delivery. Transdermal Drug Delivery Systems therapeutically effective quantity of drug across a patients skin. In order to deliver therapeutics agents through the human skin for systemic effect, the comprehensive morphological , biophysical and physicochemical properties of the skin are to be considered. Transdermal delivery provides a leading edge over injectables and oral routes by increasing patients compliance and avoiding first pass metabolism respectively. Transdermal delivery not only provides controlled, constant administration of the drug, but also allows continuous input of drugs with short biological half-lives and eliminates pulse entry into systemic circulation, which often causes undesirable side effects. Over the past decades, developing controlled drug delivery has become increasingly important in the pharmaceutical industry. The human skin surface is known to contain, on an average,10-70 hair follicles and 200-250 sweat duct on every square centimeters of the skin area. Skin penetration enhancement techniques have been developed to improve bioavailability and increase the range of drugs for which topical and transdermal delivery is viable option. The present review article explores the overall study on transdermal drug delivery (TDDS) which leads to novel drug delivery system(NDDS).

Drug Penetration Enhancement Techniques in Transdermal Drug Delivery System: A Review

Transdermal Drug Delivery System (TDDS) is described as a self-contained or discrete dosage form that is applied to the intact skin. This rout of drug administration of drugs through the skin for therapeutic use is an alternative approach to oral, intravascular, subcutaneous, and transmucosal routes. The delivery of drugs through the skin to the systemic circulation provides a convenient route of administration for a variety of clinical indications. Transdermal Drug Delivery System allows continuous drug administration, use of drugs with short biological half lives, avoids increases hepatic first pass elimination and rapid termination of medication by removing the transdermal drug delivery system from the skin. Various transdermal technologies may be applied for different categories of pharmaceuticals used for the treatment of disorders of the skin or for systemic effects to treat diseases of other organs. Several transdermal products and applications include hormone replacement therapy, contraception, pain management, angina pectoris, smoking cessation, and neurological disorders such as Parkinson's disease. The most commonly used transdermal system is the skin patch using various types of technologies. Stratum corneum is the outermost layer of the skin and it is the main barrier layer for permeation of drug in transdermal delivery of drugs. So, to circumvent the barrier properties of stratum corneum and to increase the flux of drug through skin membrane various penetration enhancement techniques are used in transdermal drug delivery system. The review presents different physical and chemical methods in penetration enhancement approaches and to optimize the transdermal delivery system.

Transdermal drug delivery an emerging approach for antipsychotics

Transdermal drug delivery system is one of the leading technology which gives extensive benefits compared to other dosage forms. In the case of drugs having a first-pass metabolism problem, small doses of drugs can be delivered. Oral drug delivery is associated with several problems like pain interrelated with the use of injections,needles, and the researchers mainly focus on the development of the transdermal route. The aim is to provide a rationale for improvement of the transdermal system of antipsychotics by highlighting the antipsychotic formulation and safely delivering medications across the skin.The present review emphasis on the latest advances in a transdermal delivery system which acts as a platform for effective transdermal delivery of antipsychotic. By using this technique, the pharmacotherapy of patients who have psychosis can be improved. There are numeral physical methods, and the skin penetration enhancement techniques have been developed that helps in delivering drugs through the skin.This technique helps to alter the barrier properties of skin and improves the penetration of the drug.It majorly highlights the possible role of microneedle in the transdermal system and acts as a different carrier in delivering several therapeutic agents effectively. This article summarizes thenovel transdermal delivery approaches, advantages, and the choice of antipsychotropic drugs.

Enhancement of skin permeability with thermal ablation techniques: concept to commercial products

Traditionally, the skin is considered as a protective barrier which acts as a highly impermeable region of the human body. But in recent times, it is recognized as a specialized organ that aids in the delivery of a wide range of drug molecules into the skin (intradermal drug delivery) and across the skin into systemic circulation (transdermal drug delivery, TDD). The bioavailability of a drug administered transdermally can be improved by several penetration enhancement techniques, which are broadly classified into chemical and physical techniques. Application of mentioned techniques together with efforts of various scientific and innovative companies had made TDD a multibillion dollar market and an average of 2.6 new transdermal drugs are being approved each year. Out of various techniques, the thermal ablation techniques involving chemicals, heating elements, lasers, and radiofrequency (RF) are proved to be more effective in terms of delivering the drug across the skin by disrupting the stratum corneum (SC). The reason behind it is that the thermal ablation technique resulted in improved bioavailability, quick treatment and fast recovery of the SC, and more importantly it does not cause any damage to underlying dermis layer. This review article mainly discussed about various thermal ablation techniques with commercial products and patents in each classes, and their safety aspects. This review also briefly presented anatomy of the skin, penetration pathways across the skin, and different generations of TDD. Graphical abstract

Potential of Sonophoresis as a Skin Penetration Technique in the Treatment of Rheumatoid Arthritis with Transdermal Patch.

Rheumatoid arthritis, a chronic disorder, limits the use of chemical penetration enhancers for a prolonged period of time. Moreover, systemic routes of administration of the first-line drug, methotrexate, have shown undesirable systemic as well as local side effects. The objective of this research was to overcome the limitations associated with treatment of rheumatoid arthritis by utilizing three physical transdermal penetration enhancement techniques namely cold-laser, electroporation, and sonophoresis to deliver methotrexate. Methotrexate patch was prepared using solvent casting method and the ex-vivo release of methotrexate in combination with three physical penetration enhancers (sonophoresis, electroporation, and cold laser) were studied. The best technique was employed in pre-clinical testing in arthritic and control groups of male Wistar rats excluding remaining two techniques. The comparative ex-vivo studies showed that the penetration enhancement of methotrexate is maximum by sonophoresis followed by electroporation and cold laser (sonophoresis > electroporation > cold laser). In pharmacodynamic studies, the reduction in diameter of injected and non-injected paw on day 5 and day 21 for group 4 (ultrasound pre-treated group) was higher as compared to group 3 (group receiving only methotrexate patch). The motility score and the reduction in pain were significantly improved for group 4 than group 3 on both day 5 and day 21 (P˂0.05) which confirmed the faster recovery of animals of group 4 due to penetration enhancement of methotrexate patch by ultrasound treatment. From the results, it can be concluded that sonophoresis along with methotrexate patch has shown a significant effect in the treatment of rheumatoid arthritis.

Hyaluronic Acid-Based Dissolving Microneedle Patch Loaded with Methotrexate for Improved Treatment of Psoriasis.

Methotrexate (MTX) is one of the first-line treatments for moderate to severe psoriasis, while the side effects caused by injection and oral administration of MTX greatly restrict its clinical application. Transdermal drug delivery offers a desirable alternative to the conventional approaches, but the performances of the currently available skin penetration enhancement techniques are not so satisfactory. To address these limitations, we developed a dissolving microneedle (MN) patch made of hyaluronic acid (HA) with excellent water solubility, biocompatibility, biodegradability, and mechanical properties. The amount of MTX encapsulated in the needles of the patch could be controlled during the fabrication process for precise dosage. Interestingly, the MTX-loaded MNs successfully penetrated imiquimod (IMQ)-induced thickened epidermis in mice and delivered the drug intralesionally. Meanwhile, fast dissolution of HA endowed the MNs with operability for patients. We found that the MTX-loaded MNs not only showed well-maintained inhibitory effect in vitro but also alleviated the psoriasis-like skin inflammation in mice. Moreover, the MTX-loaded MNs were significantly more efficacious than taking the same dose of drug orally. Consequently, a higher oral dose of MTX was required for a comparable amelioration, which in turn increased its systemic toxicity. Taken together, the proposed MTX-loaded dissolving MN patch strategy provides a new opportunity for efficient and safe treatment of psoriasis.

Drug penetration enhancement techniques in ablative fractional laser assisted cutaneous delivery of indocyanine green.

Background and ObjectivesTopical drug delivery can be increased by pretreatment of the skin with ablative fractional laser (AFXL). Several physical penetration enhancement techniques have been investigated to further improve AFXL‐assisted drug delivery. This study investigated the influence of three of these techniques, namely massage, acoustic pressure wave treatment, and pressure vacuum alterations (PVP) on the distribution of the fluorescent drug indocyanine green (ICG) at different depths in the skin after topical application on AFXL pretreated skin.Materials and MethodsIn ex vivo human skin, test regions were pretreated with AFXL (10,600 nm, channel depth 300 μm, channel width 120 μm, density 15%). Subsequently, ICG was applied, followed by massage, acoustic pressure wave treatment or PVP. ICG fluorescence intensity (FI) was assessed after 1, 3, and 24 hours at several depths using fluorescence photography.ResultsFI was higher when using enhancement techniques compared to control (AFXL‐only) up to 3 hours application time (P < 0.05). After 3 hours, mean surface FI was highest after acoustic pressure wave treatment (61.5 arbitrary units; AU), followed by massage (57.5AU) and PVP (46.9AU), respectively (for comparison: AFXL‐only 31.6AU, no pretreatment 14.9AU). Comparable or higher FI was achieved already after 1 hour with enhancement techniques compared to 3–24 hours application time without. After 24 hours, no significant differences between enhancement techniques and AFXL‐only were observed (P = 0.31).ConclusionPenetration enhancement techniques, especially acoustic pressure wave treatment and massage, result in improved drug accumulation in AFXL‐pretreated skin and reduce the application time needed. Lasers Surg. Med. © 2019 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

AN OVERVIEW OF TRANSDERMAL DELIVERY SYSTEM

Recently, most widely using conventional dosage form such as tablet, capsules, and injections but due to some case we are preferable to choose transdermal drug delivery system (TDDS) because conventional oral dosage form undergo first pass metabolism. In TDDS, skin is the effective medium for the penetration of drug into systemic circulation. This system required very low dose for the effective result or action. One of the major disadvantages of TDDS is penetration rate is very low through the stratum corneum. Nowadays, different types of skin penetration enhancement techniques are used for increasing the penetration. These types of techniques can be also increase the bioavailability. The patients have more preferable to choose this type of drug delivery system because it has more advantages than conventional dosage form. This article is discuses about the anatomy and physiology of skin and its drug penetration capacity, polymers used in transdermal drug delivery and different types of TDDS.

PHYSICAL APPROACH TO TRANSDERMAL DRUG DELIVERY: A REVIEW

Transdermal drug delivery system (TDDS) is the topically administered medication, which when applied to the skin, delivers the drug through the skin for systemic effect at a predetermined and controlled rate. For the drugs, having the short biological half-life, transdermal drug delivery system is convenient. It overcomes the problems like the hepatic first pass effect, improves the compliance of patients, decreases the administration frequency, and reduce the gastrointestinal side effects, peak and valley levels in the blood are avoided. Due to having an advantage of being non-invasive, this delivery has to fulfill some parameters such as high potency, better permeability through skin and non-irritation for better compliance. Skin serves as a site of drug application for local effect as well as systemic effect. There are wide varieties of drugs for which topical or transdermal is a viable option, skin penetration enhancement techniques have been developed for such drugs. There are a number of physical methods to increase drug delivery via the skin, many of which require the use of devices and some of which hold the promise to significantly expand the spectrum of drugs that can be administered transdermally to include water-soluble molecules and macromolecules. Iontophoresis and electroporation represent electrically assisted, physical approaches to enhance delivery of drugs/macromolecules across the stratum corneum. This review highlights the detailed role of physical penetration and describes their mechanism of action. Keywords: transdermal drug delivery system, stratum corneum, skin penetration enhancer, physical enhancer, iontophoresis.

Skin penetration enhancer's in transdermal drug delivery systems

Transdermal drug delivery is one of the most potential methods for drug application. Though the skin, in particular the stratum corneum, possesses a dreadful barrier to drug penetration thus limiting topical and transdermal bioavailability. So skin penetration enhancement techniques have been developed to improve bioavailability and to increase the range of drugs, the topical and transdermal delivery is a viable option. The technique is generally non-invasive, well accepted by patients and can be used to provide local delivery over several days. Various chemical enhancers are used to improve bioavailability of the drugs such as sulfoxides, fatty acids, azones and non ionic surfactants. This review article presents the comprehensive different aspects of drug delivery by transdermal route with various chemical penetration enhancers.

Lopinavir metered-dose transdermal spray through microporated skin: Permeation enhancement to achieve therapeutic needs

A user friendly metered-dose transdermal spray (MDTS) of Lopinavir was developed and a combination of chemical and physical penetration enhancement techniques was utilized to enhance overall drug permeation across skin. Formulation was optimized varying Kollidon® VA 64 level while optimized batch was exhaustively characterized for in vitro drug release, ex vivo skin permeation and in vivo bioavailability. Safety and stability were also ascertained. Formulation containing 5 %w/v of Kollidon® had best sprayability and volatilization property. A significantly high permeation enhancement ratio (1.77) and steady state transdermal flux (52.5 μg/cm2/h) through microporated pig ear skin ex vivo indicated the permeation enhancement potential of the techniques applied. A remarkable 3-fold rise in relative bioavailability via transdermal route (FMDTS via microporated skin = 291.15%) as compared to oral suspension of marketed tablet (AUC0−∞ = 45.94 h*μg/ml) further confirmed the validity of our hypothesis. The outcomes of in vitro, ex vivo and in vivo characterization of Lopinavir MDTS represented the system as safe, effective and stable which seems promising for their extended clinical evaluation.

Recent Advances in Permeation Enhancement Techniques for Transdermal Drug Delivery Systems: A Review

Transdermal route is preferred due to its numerous advantages over other routes. Stratum corneum and other skin layers are the foremost obstacles in employing skin as a drug delivery route. So various penetration enhancement techniques are utilized which cause the delivery of drug through the skin in proper amounts and at a predetermined rate. Permeation enhancers are the agents which do not have any therapeutic activity themselves but these increase the permeability of drug through the skin. Numerous chemical agents from natural and synthetic origins are evaluated for their penetration enhancement ability. Other than chemical agents, various novel drug delivery systems such as nanoparticles, liposomes, niosomes, transferosomes and ethosomes etc; and various physical means of skin ablaze are also useful for drug penetration through skin. The focus of this review is to discuss various permeation enhancement techniques for effective delivery of drugs through skin.

Recent Advances in Physical Approaches for Transdermal Penetration Enhancement

Transdermal delivery offers opportunities for inventive, challenging and valuable research with patient benefits. However, the prominent challenge in designing transdermal drug delivery systems is to overcome the natural transport barrier of the skin, the stratum corneum. Several physical and chemical enhancement techniques have been investigated in the last decade to breach the skin barrier and assist the transport of macromolecules across skin. Recent technological advances in this field include novel combination strategies of penetration enhancement techniques, microneedle array designs, needle-free technologies, nanocarriers, metered dose and microstructured transdermal systems. The present review reports on recent advances in physical approaches towards enhanced transdermal penetration. Enhancement strategies comprehensively covered in this review emphasize the significant achievements gained through successful transdermal delivery of hydrophilic macromolecules, vaccines, proteins, peptides, oligonucleotides, fluorescent dyes and plasmid delivery. Some commercially available technologies for transdermal delivery have also been covered. These novel technologies hold immense potential to advance further into clinical practice and enable better therapeutic applications and prophylactic interventions for various diseases.

Electroporation: An Avenue for Transdermal Drug Delivery

The stratum corneum (SC) is a primary rate limiting barrier to permeation of drug molecules through the skin. Small molecular weight lipophilic drugs that are effective at low doses can be effectively delivered by passive transdermal delivery. The SC does not permit passage of polar/hydrophilic and macromolecules. Passive and physical penetration enhancements strategies are used to overcome this barrier property of the SC. Passive penetration enhancement techniques include use of supersaturated solutions and penetration enhancers. In general, the drug delivery potential of chemical modalities is limited. Therefore, physical permeation enhancement techniques gained a lot of focus in the recent past. Physical penetration enhancement techniques include iontophoresis, electroporation and sonophoresis. Electroporation utilizes high voltage pulses that are applied for a very short time to permeabilize the skin to facilitate transport of macromolecules and hydrophilic compounds. Several drugs have been administered via this system successfully. This review presents an overview of in-vitro and in-vivo studies demonstrating therapeutic benefits offered by electroporation assisted permeation. Factors affecting electroporation, synergism between electroporation and other penetration enhancing strategies are also discussed.

Physical and chemical penetration enhancers in transdermal drug delivery system

There is considerable interest in the skin as a site of drug application for both local and systemic effect. However, the skin, in particular the stratum corneum, possesses a formidable barrier to drug penetration thereby limiting topical and transdermal bioavailability. Skin penetration enhancement techniques have been developed to improve bioavailability and to increase the range of drugs for which topical and transdermal delivery is a viable option. The permeation of drug through skin can be enhanced by both chemical penetration enhancement and physical methods. In this review, we have discussed the physical and chemical penetration enhancement technology for transdermal drug delivery as well as the probable mechanisms of action.

Transdermal Drug Delivery: Penetration Enhancement Techniques

There is considerable interest in the skin as a site of drug application both for local and systemic effect. However, the skin, in particular the stratum corneum, poses a formidable barrier to drug penetration thereby limiting topical and transdermal bioavailability. Skin penetration enhancement techniques have been developed to improve bioavailability and increase the range of drugs for which topical and transdermal delivery is a viable option. This review describes enhancement techniques based on drug/vehicle optimisation such as drug selection, prodrugs and ion-pairs, supersaturated drug solutions, eutectic systems, complexation, liposomes, vesicles and particles. Enhancement via modification of the stratum corneum by hydration, chemical enhancers acting on the structure of the stratum corneum lipids and keratin, partitioning and solubility effects are also discussed. The mechanism of action of penetration enhancers and retarders and their potential for clinical application is described.

Penetration enhancement of transdermal delivery--current permutations and limitations.

In order to achieve enhanced topical drug delivery, it is necessary to make physical or biomolecular structural alterations to the stratum corneum by suitable techniques or by the use of specific chemical agents or drug carriers. The role of the chemical penetration enhancer is to reversibly alter the barrier properties of the stratum corneum by disruption of the membrane structures or by maximizing drug solubility within the skin. Alternatively, permeant delivery to the dermal vasculature using one of several physical methods to reduce diffusional resistance within the skin may be used to promote drug penetration. In the present article, we summarize the major facets of the diverse spectrum of penetration enhancement techniques that include modification of the stratum corneum, lipid-based delivery systems, drug/vehicle interactions, bypassing the stratum corneum, and electrical techniques of enhancement.