Transdermal Research Articles

Comminution technologies in the pharmaceutical industry: a comprehensive review with recent advances

Abstract Comminution processes play a pivotal role in diverse applications, ranging from food processing, to mining and materials engineering. The pharmaceutical industry is no exception, with an increased focus on particle engineering to overcome the growing challenges related to the complexity of new drug molecules such as poor water solubility or stability issues. Additionally, the preparation of powders for pulmonary, transdermal, topical, ophthalmic, oral or parenteral administration often requires specific particle size requirements. Thus, milling technologies offer an excellent option for controlling particle size, improving the stability, dissolution, absorption rate, and bioavailability of poorly water-soluble drugs. They also contribute to enhancing pharmaceutical forms and overall product performance. This review highlights the different types of technologies used for comminution, the respective advantages and drawbacks, as well as connected topics including feed material properties, analytical techniques, process analytical technology, process safety, new top-down technologies and key information to consider when selecting a technology. Thus, an in-depth approach of comminution in the pharmaceutical industry is presented. This compilation serves as a source of comprehensive information for those who decide to initiate research projects in this field, or to update their existing literature knowledge and understanding.

Mitigating Paxlovid™-induced drug‒drug interaction toxicity: an in silico insight

The clinical drug-drug interaction side-effects of Ritonavir, an ingredient in Paxlovid™, have been documented, highlighting the need to explore alternative administration methods for Nirmatrelvir, another drug in the Paxlovid™ combination. In this study, the skin permeability potential of Nirmatrelvir was assessed using various in silico models. The prediction results suggest that Nirmatrelvir could be administrated via the transdermal route, offering a promising avenue to enhance the efficacy of anti-COVID-19 agents.

The Effects of Single Testosterone Administration and Stress Induction on Steroid Hormone Levels in Hair

Hair steroid analysis is increasingly recognized for its ability to capture cumulative hormone secretion, thought to reflect an individual’s response to long-term environmental conditions. Despite its growing use, the influence of single, isolated events on hair steroid concentrations remains underexplored. Our study therefore examined the effects of a single-dose transdermal testosterone administration (150mg) and acute laboratory stress induction on hair testosterone and cortisol levels in a randomized, between-subject, placebo-controlled, and double-blind design. Liquid chromatography-tandem mass spectrometry analysis revealed a significant increase in hair testosterone levels seven weeks post-testosterone administration, underscoring the efficacy of hair analysis in detecting single-use hormone intake. Moreover, we observed a significant elevation in hair cortisol levels seven weeks post-exposure to the laboratory somatic stressor (Cold pressor test), highlighting the efficacy of hair analysis in capturing experimentally induced hormonal responses. The exploration of contextual factors revealed that individuals in committed relationships exhibited lower levels of both hair cortisol and testosterone compared to those who were single or in uncommitted relationships.Our study provides new insights into the sensitivity of hair analysis for detecting hormonal changes following single-dose hormone administration and experimentally induced short-term stress events. The exploratory findings emphasize the importance of individual contextual factors in influencing hair hormone concentrations and lay the groundwork for further investigation into the dynamics of cumulative hair hormone measurements.

Transdermal contraception and quality of life

Analysis of the current demographic situation in Ukraine in recent years indicates the presence of a deep demographic crisis on the background of social and economic problems and the military-political situation. In such conditions, one of the aspects of the country’s effective demographic policy should be the improvement of women’s reproductive health which depends on the abortion rate.In Ukraine the frequency of abortions has decreased significantly in recent years and today it is 4.6 per 1,000 women of fertile age, while the rate of childbirth exceeds the rate of abortions. Such outcome is the result of the effective use of modern family planning methods, including hormonal contraception. The patch which contains norelgestromin and ethinyl estradiol is the only contraceptive in Europe with transdermal hormone administration. With its use it is possible to ensure a constant level of ethinyl estradiol and norelgestromin in a woman’s blood without peaks and troughs by passing the digestive tract.The objective: to compare the impact on the quality of life of women, as well as the effectiveness, safety and convenience of using a patch containing norelgestromin and ethinylestradiol with a combined oral contraceptive in women of reproductive age.Materials and methods. 266 women of reproductive age who needed reliable contraception and used various modern hormonal methods of contraception were followed up through 2022.The women were divided into the following clinical groups: I group (main group; n=133) – healthy women of fertile age who used a transdermal hormonal system containing norelgestromin 6.0 mg, ethinyl estradiol 0.60 mg for the contraception; II group (comparison group; n=133) – healthy women of fertile age who used a combined oral contraceptive (ethinyl estradiol 0.02 mg and drospirenone 3 mg in a 24+4 regimen) for the contraception.Evaluation of efficiency, safety, convenience was carried out according to the Perl index, data from the FSFI questionnaire (Female sexual function index), the SF-36 quality of life scale.Results. The results demonstrated that hormonal patch, which contains norelgestromin and ethinyl estradiol, is a highly effective contraceptive drug and does not affect the parameters of hormonal and non-hormonal homeostasis, and is well tolerated by women.During the study the use of transdermal contraception in women of reproductive age prevented unplanned pregnancy in 100 % of cases. Evaluating the convenience of the contraceptive method on a five-point scale, women who used the hormonal patch have estimated the convenience with an average score of 4.98±0.02 points; in the group of women who used combined oral contraceptives, the result of convenience was significantly lower: the average score was 4.3±0.03 points (p<0.05).The transdermal form of the contraceptive avoids the effect of “first passage” through the liver, as a result, women who used transdermal contraception had 3.5 times less complications of the digestive tract.Conclusions. Hormonal patch containing norelgestromin and ethinylestradiol is a modern, easy-to-use and reliable method of hormonal contraception for women of reproductive age. It allows you to avoid the effect of “first passage” through the liver, complications of the digestive tract and thrombosis.The constant level of ethinyl estradiol and norelgestromin in a woman’s blood, which this patch provides, makes it possible to improve the psycho-emotional state, increase libido and positively affects the quality of life of women of reproductive age.

A systematic review of microneedles technology in drug delivery through a bibliometric and patent overview

The transdermal drug delivery (TDD) route has gathered considerable attention for its potential to improve therapeutic efficacy while minimizing systemic side effects. Among transdermal technologies, microneedle (MN) devices have proven to be a promising approach that combines the advantages of traditional needle injections and non-invasive topical applications. This review provides a comprehensive analysis of progress in transdermal drug delivery systems (TDDS) via MN from 2000 to 2023, integrating bibliometric analysis and patent landscape to present a multi-faceted perspective on the evolution of this technology. The study identifies key trends, challenges, and opportunities in the research, implementation, and commercialization of MN tools through a systematic examination of scientific literature and an extensive investigation of global patent databases. The study of bibliometric trends reveals the leading experts, organizations, companies, and countries contributing to this field, collaboration networks, and the thematic evolution of research topics. The patent analysis offers insights into innovative trajectories, key players, and geographical distribution of intellectual property. This review resumes the latest advancements in MN devices and provides a strategic outlook that can guide future research directions, promote partnerships, and inform stakeholders involved in the development of TDDS.

Estradiol modulates resting-state connectivity in perimenopausal depression

The perimenopausal transition is marked by an increased risk for affective dysregulation and major depressive disorder (MDD), with hormone replacement therapy using estradiol (E2) showing promise for alleviating symptoms of perimenopausal-onset MDD (PO-MDD). Although E2's effectiveness is recognized, its mechanisms underlying mood symptom modulation remain to be fully elucidated. Building on previous research suggesting that E2 may influence mood by altering cortico-subcortical connectivity, this study investigated the effects of transdermal E2 on resting-state functional connectivity (rsFC) in perimenopausal women with and without PO-MDD, focusing on rsFC changes using seed regions within reward and emotion processing networks. In this pharmaco-fMRI study, 16 participants with PO-MDD and 18 controls underwent rsFC analysis before and after three weeks of transdermal E2 administration. Pre-E2 results showed that the PO-MDD group, compared to controls, exhibited increased connectivity between the right amygdala (seed) and medial prefrontal cortex and anterior cingulate cortex, and decreased connectivity with the supplementary motor area. Comparing groups on change from pre-E2 to post-E2 revealed several significant E2-induced changes in connectivity between the PO-MDD and control groups: PO-MDD showed increased connectivity between the right caudate nucleus (seed) and left insula, and decreased connectivity between the right putamen (seed) and left hippocampus, and the right amygdala (seed) and left ventromedial prefrontal cortex. Notably, changes in connectivity were predictive of symptom trajectories across anhedonia, depressive mood, somatic, and vasomotor domains in the PO-MDD group. These findings enrich our understanding of PO-MDD by highlighting distinct rsFC patterns characteristic of the disorder and their shifts in response to E2 treatment, suggesting potential neural mechanisms underlying E2's mood-modulating effects.

Validation of two enzyme immunoassays for non-invasive glucocorticoid measurement in a lacertid lizard (Podarcis muralis): effects of pharmacological and biological stimuli on faecal corticosterone metabolites and behaviour.

The assessment of stress-related hormone levels using non-invasive methods has gained popularity in mammal and bird welfare, yet its application in reptiles remains limited. Particularly, the exploration of physiological measures such as faecal corticosterone metabolites (FCMs) for reptilian welfare has scarcely been explored. This study aims to validate two enzyme immunoassays (5α-pregnane-3ß,11ß,21-triol-20-one and 11-oxoaetiocholanolone EIA) for monitoring FCM levels in the European common wall lizard (Podarcis muralis). We collected daily faecal samples before (baseline) and after (post-treatment phase) inducing elevated corticosterone levels using transdermal administration of corticosterone (pharmacological treatment) and handling/confinement (biological treatment). We also conducted daily behavioural observations to explore the relationship between stress-related corticosterone changes and behaviour. Although treatments induced significant increases in FCM levels, the effect was much larger in the pharmacological one. Transdermal corticosterone induced a cumulative increase in FCMs over the treatment period, with a higher response observed in females. In contrast, the biological treatment yielded smaller FCM peaks, with no significant sex differences. Overall, 5α-pregnane-3ß,11ß,21-triol-20-one EIA appeared to be more sensitive in detecting these effects. Regarding lizard behaviour, both treatments led to increased hiding and decreased basking compared to baseline. The effects were more pronounced in animals subjected to handling/confinement, despite smaller FCM increases. Our results confirm the suitability of an EIA for monitoring FCMs in both male and female common wall lizards and provide insights into the complexities of using integrated approaches to assess stress, highlighting the need for further research on direct measures to evaluate reptile welfare.

Hypothesizing the Oleic Acid-Mediated Enhanced and Sustained Transdermal Codelivery of Pregabalin and Diclofenac Adhesive Nanogel: A Proof of Concept.

Pregabalin (PG) and diclofenac diethylamine (DEE) are anti-inflammatory molecules that are effective in relieving inflammation and pain associated with musculoskeletal disorders, arthritis, and post-traumatic pain, among others. Intravenous and oral delivery of these two molecules has their limitations. However, the transdermal route is believed to be an alternate viable option for the delivery of therapeutic molecules with desired physicochemical properties. To this end, it is vital to understand the physicochemical properties of these drugs, dosage, and strategies to enhance permeation, thereby surmounting the associated constraints and concurrently attaining a sustained release of these therapeutic molecules when administered in combination. The present work hypothesizes the enhanced permeation and sustained release of pregabalin and diclofenac diethylamine across the skin, entrapped in the adhesive nano-organogel formulation, including permeation enhancers. The solubility studies of pregabalin and diclofenac diethylamine in combination were performed in different permeation enhancers. Oleic acid was optimized as the best permeation enhancer based on in vitro studies. Pluronic organogel containing pregabalin and diclofenac diethylamine with oleic acid was fabricated. Duro-Tak® (87-2196) was added to the organogel formulation as a pressure-sensitive adhesive to sustain the release profile of these two therapeutic molecules. The adhesive organogel was characterized for particle size, scanning electron microscopy, and contact angle measurement. The HPLC method developed for the quantification of the dual drug showed a retention time of 3.84 minutes and 9.69 minutes for pregabalin and diclofenac, respectively. The fabricated nanogel adhesive formulation showed the desired results with particle size and contact angle of 282 ± 57 nm and ≥120⁰, respectively. In vitro studies showed the percentage cumulative release of 24.90 ± 4.65% and 33.29 ± 4.81% for pregabalin and diclofenac, respectively. In order to accomplish transdermal permeation, the suggested hypothesis of fabricating PG and DEE nano-organogel in combination with permeation enhancers will be a viable drug delivery method. In comparison to a traditional gel formulation, oleic acid as a permeation enhancer increased the penetration of both PG and DEE from the organogel formulation. Notably, the studies showed that the use of pressure-sensitive adhesives enabled the sustained release of both PG and DEE.Therefore, the results anticipated the hypothesis that the transdermal delivery of adhesive PG and DEEbased nanogel across the human skin can be achieved to inhibit inflammation and pain.

A Review: Bilosomes as Nanocarriers

Abstract: Liposomes and niosomes, two vesicular carriers that are prospective candidates for drug delivery, have been used in numerous formulations. New research in this area has led to the development of a ‘niosome-like’ colloidal carrier termed bilosomes. Bilosomes have been designed as prospective vesicular carriers to deliver targeted drugs via parenteral, transdermal, and oral routes. These innovative vesicular systems, based on bile salts, have been discussed in detail in the current review. The review addresses the composition of bilosomes, their creation and characterization processes. Previous research on bilosomes has been compiled, along with their applications and advantages over more traditional nanocarriers such as liposomes and niosomes. It also emphasizes the utilization of bilosomes and their stability.

Differences in Anti-inflammatory Effects of Celecoxib Emulgel Preparations with Variations in Surfactant Concentration between Lecithin and Tween 80

Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) which is widely used to treat inflammation such as rheumatoid arthritis and primary dysmenorrhea. The absorption of celecoxib in the body is very low when taken orally, so it can be increased by changing the route of administration via transdermal route such as emulgel. This study aims to determine the increase in the anti-inflammatory activity of celecoxib emulgel with varying concentrations of surfactants in formula with Lecithin and formula with Tween 80. Celecoxib emulgel, was made into 3 formulas with variations in the concentration for each formula with Lecithin (FI=3%; FII=5%; FIII=7%) and Tween 80 (FI=5%; FII=10%; FIII=15%). The anti-inflammatory activity test was carried out by inducing edema in the soles of rats' feet using carrageenan. Rats were divided into 5 groups for each formula: 1) negative control, 2) without surfactant, 3) FI, 4) FII, and 5) FIII. The edema volume was measured every 1 hour for 6 hours using a plethysmometer. Results of the anti-inflammatory test showed that the average value of AUC0-360 in the Lecithin group = 57.97-77.17 μg/hour/mL and in the Tween 80 group = 51.45-77.17 μg/hour/mL. %DAI results of formula without surfactant=9.33%, FI (Lecithin=10.01%; Tween 80=24.49%), FII (Lecithin=18.36%; Tween 80=29.05%), and FIII (Lecithin=24.88%; Tween 80=33.33%). Based on these data, it can be concluded that there is an increase in the anti-inflammatory effect of celecoxib emulgel with increasing surfactant concentration in the formula with Lecithin and in the formula with Tween 80. Keywords: Anti-inflammatory; celecoxib; emulgel; surfactant

A macromolecule infliximab loaded reverse nanomicelles-based transdermal hydrogel: An innovative approach against rheumatoid arthritis

Infliximab (IFX) is used as a biotherapeutic agent for the treatment of rheumatoid arthritis (RA); however, its biological activity is lost orally because of variations in gastric pH and enzymatic degradation, and reduced bioavailability. The authors have tried to improve the efficacy of macromolecule delivery through transdermal route. Polycaprolactone-Polyethylene glycol-Polycaprolactone (PCL-PEG-PCL) triblock copolymer previously synthesized and was used as an efficient carrier for the preparation of IFX loaded reverse nanomicelles (IFX-RNMs). The RNMs were fabricated via nanoprecipitation technique, characterized and then were incorporated into a Carbopol-based hydrogel with eucalyptus oil (EO) as a penetration enhancer. The optimized RNMs had a particle size of 72.32 nm and an encapsulation efficiency of 83 %. In vitro release, exhibited a sustained pattern of IFX from the prepared carrier system, ex-vivo skin permeation and fluorescence microscopic studies revealed that IFX-RNMs loaded hydrogel with EO markedly improved permeation. An in vivo study was carried out on a CFA-induced RA mice model that revealed significant improvements in the results of behavioral parameters, biochemical assays, histopathological and radiological analysis. Overall, the results concluded that the IFX-RNMs loaded hydrogel can be used as a suitable approach for treating RA.

Development of a Physiologically Based Pharmacokinetic Model for Flunixin in Cattle and Swine Following Dermal Exposure.

Flunixin meglumine is a nonsteroidal anti-inflammatory drug (NSAID). Banamine® Transdermal is a pour-on formulation of flunixin approved for pain control in beef and dairy cattle, but not for calves and some classes of dairy cattle or swine. Violative flunixin residues in edible tissues in cattle and swine have been reported and are usually attributed to non-compliant drug use or failure to observe an appropriate withdrawal time. This project aimed to develop a physiologically based pharmacokinetic (PBPK) model for flunixin in cattle and swine to predict withdrawal intervals (WDI) after exposures to different therapeutic regimens of Banamine® Transdermal. Due to the lack of comprehensive skin physiological data in cattle, the model was initially developed for swine and then adapted for cattle. Monte Carlo simulation was employed for population variability analysis. The model predicted WDIs were rounded to 1 and 2 days for liver and muscle in cattle, respectively, under FDA tolerance levels, while under EU maximum residue limits (MRLs), the WDIs were rounded to 1, 3, 2, and 2 days for liver, kidney, muscle, and fat, respectively, following a labeled single transdermal 3.3 mg/kg dose in cattle. The model was converted into a user-friendly interactive PBPK (iPBPK) interface. This study reports the first transdermal absorption model for drugs in cattle. This iPBPK model provides a scientifically based tool for the prediction of WDIs in cattle and swine administered with flunixin in an extra-label manner, especially by the transdermal route.

A Comprehensive Review of the Evaluation of in Situ Gels

In situ gels are now among the most widely used and widely available systems. These systems minimize drug administration frequency because of their special sol-to-gel transition properties, increasing patient comfort. Other benefits of these systems include easy production, improved adherence, and ease of use. 'Sol-gel' produces a colloidal suspension or solution by hydrolyzing the precursor and then polymerizing it through condensation. These in situ gelling techniques gel at the accomplishment site because they can be administered as solutions. Recently, several researchers developed liposomes, microspheres, nanoemulsions, nanospheres, and other in situ gelling systems. One of the greatest innovative drug delivery methods to date is the "in situ gel" system, which promotes better patient comfort and compliance as well as a prolonged and regulated release of the medication. With in situ gel formation, a variety of natural and synthetic polymers may find application in oral, ophthalmic, transdermal, buccal, intraperitoneal, parenteral, injectable, rectal, and vaginal routes. Research on the in-situ gel system has a lot of potential to offer cutting-edge methods for medication delivery systems.

Silk fibroin microneedles loaded with epigallocatechin gallate mitigate atrazine-induced testicular toxicity

Atrazine (ATZ), a commonly used herbicide, disrupts male endocrine systems, impacting reproductive health. Epigallocatechin gallate (EGCG) possesses potent antioxidant properties and shows promise in alleviating testicular dysfunction induced by endocrine disruptors. However, its clinical utility is hindered by poor physicochemical stability and low oral bioavailability. Herein, we first developed a silk fibroin microneedles (MNs) patch loaded with EGCG, enabling EGCG to directly target the testes through transdermal administration. Our findings revealed that EGCG-loaded silk fibroin microneedles (EGCG-SF-MNs) exhibited excellent biocompatibility with no observed cytotoxicity in vitro or in vivo. In vitro assays revealed that EGCG-SF-MN patches significantly reduced ATZ-induced apoptosis and oxidative stress in GC-1 spg cells by modulating the Bcl-2/Bax ratio and ROS levels. In vivo studies in rats further confirmed the therapeutic potential of these patches, as they reversed ATZ-induced testicular dysfunction, sperm abnormalities, and blood-testis barrier disruption. Proteomics analysis highlighted the beneficial effects of EGCG-SF-MN patches on restoring protein expression altered by ATZ, particularly in necroptosis and lysosome pathways. Collectively, the development of EGCG-SF-MNs demonstrates enhanced therapeutic and targeted delivery efficacy for potential clinical applications in treating male reproductive disorders induced by environmental endocrine disruptor ATZ.

Nanostructured Lipid Carrier-based Topical Gels as Novel Drug Delivery System: A Comprehensive Overview.

Nanostructured lipid carriers (NLCs) are lipidic nanocarriers that recover the permanency and capacity of drug payloads. NLCs are well-known as second-generation lipid nanocarriers with an unstructured matrix, presenting potentially advantageous nanocarrier systems with marketable opportunities because of reproducible production methodologies and biocompatible lipidic excipients. These (NLCs) are now recognized as a very promising nanocarrier structure for the efficient delivery of drugs via different administration routes. In recent years, several NLC-based gels have been developed and evaluated for topical delivery of many drugs and other therapeutic agents. This review article presents an overview of NLC-based topical gels investigated to deliver drugs via ocular, dermal, and transdermal routes. In addition, the classification, manufacturing, characterizations, advantages, and disadvantages of NLCs are addressed in this article. We also discussed different evaluations of NLC-based topical gels.

Strategies for transportation of peptides across the skin for treatment of multiple diseases.

An established view in genetic engineering dictates an increase in the discovery of therapeutic peptides to enable the treatment of multiple diseases. The use of hypodermic needle for delivery of proteins and peptides occurs due to the hydrophilic nature, sensitivity toward proteolytic enzymes and high molecular weight. The non-invasive nature of the transdermal delivery technique offers multiple advantages over the invasive route to release drugs directly into the systemic circulation to enhance bioavailability, better patient compliance, reduced toxicity and local irritability. The transdermal route seems highly desirable from the pharmaco-therapeutic and patient compliance point of view, however, the lipophilic barrier of skin restricts the application. The use of several techniques like electrical methods (iontophoresis, sonophoresis etc.), chemical penetration enhancers (e.g. protease inhibitors, penetration enhancers, etc.) and nanocarriers (dendrimers, lipid nanocapsules, etc.) are utilized to improve the passage of drug molecules across the biomembranes. Additionally, such clinical interventions facilitate the physicochemical characteristics of peptides, to enable effective preservation, conveyance and release of therapeutic agents. Moreover, strategies ensure the attainment of the intended targets and enhance treatment outcomes for multiple diseases. This review article focuses on the techniques of peptide transportation across the skin to advance the delivery approaches and therapeutic efficiency.

Molecular dynamics simulations of lipid composition and its impact on structural and dynamic properties of skin membrane

The stratum corneum (SC) plays the most important role in the absorption of topical and transdermal drugs. In this study, we developed a multi-layered SC model using coarse-grained molecular dynamics (CGMD) simulations of ceramides, cholesterol, and fatty acids in equimolar proportions, starting from two different initial configurations. In the first approach, all ceramide molecules were initially in the hairpin conformation, and the membrane bilayers were pre-formed. In the second approach, ceramide molecules were introduced in either the hairpin or splayed conformation, with the lipid molecules randomly oriented at the start of the simulation. The aim was to evaluate the effects of lipid chain length on the structural and dynamic properties of SC. By incorporating ceramides and fatty acids of different chain lengths, we simulated the SC membrane in healthy and diseased states. We calculated key structural properties including the thickness, normalized lipid area, lipid tail order parameters, and spatial ordering of the lipids from each system. The results showed that systems with higher ordering and structural integrity contained an equimolar ratio of ceramides (chain length of 24 carbon atoms), fatty acids with chain lengths ≥ of 20 carbon atoms, and cholesterol. In these systems, strong apolar interactions between the ceramide and fatty acid long acyl chains restricted the mobility of the lipid molecules, thereby maintaining a compact lipid headgroup region and high order in the lipid tail region. The simulations also revealed distinct flip-flop mechanisms for cholesterol and fatty acid within the multi-layered membrane. Cholesterol is mostly diffused through the tail-tail interface region of the membrane and could flip-flop in the same bilayer. In contrast, fatty acids flip-flopped between adjacent leaflets of two bilayers in which the tails crossed the thinner headgroup region of the membrane. To conclude, our SC model provides mechanistic insights into lipid mobility and is flexible in its design and composition of different lipids, enabling studies of varying skin conditions.

The Design Features, Quality by Design Approach, Characterization, Therapeutic Applications, and Clinical Considerations of Transdermal Drug Delivery Systems—A Comprehensive Review

Transdermal drug delivery systems (TDDSs) are designed to administer a consistent and effective dose of an active pharmaceutical ingredient (API) through the patient’s skin. These pharmaceutical preparations are self-contained, discrete dosage forms designed to be placed topically on intact skin to release the active component at a controlled rate by penetrating the skin barriers. The API provides the continuous and prolonged administration of a substance at a consistent rate. TDDSs, or transdermal drug delivery systems, have gained significant attention as a non-invasive method of administering APIs to vulnerable patient populations, such as pediatric and geriatric patients. This approach is considered easy to administer and helps overcome the bioavailability issues associated with conventional drug delivery, which can be hindered by poor absorption and metabolism. A TDDS has various advantages compared to conventional methods of drug administration. It is less intrusive, more patient-friendly, and can circumvent first pass metabolism, as well as the corrosive acidic environment of the stomach, that happens when drugs are taken orally. Various approaches have been developed to enhance the transdermal permeability of different medicinal compounds. Recent improvements in TDDSs have enabled the accurate administration of APIs to their target sites by enhancing their penetration through the stratum corneum (SC), hence boosting the bioavailability of drugs throughout the body. Popular physical penetration augmentation methods covered in this review article include thermophoresis, iontophoresis, magnetophoresis, sonophoresis, needle-free injections, and microneedles. This review seeks to provide a concise overview of several methods employed in the production of TDDSs, as well as their evaluation, therapeutic uses, clinical considerations, and the current advancements intended to enhance the transdermal administration of drugs. These advancements have resulted in the development of intelligent, biodegradable, and highly efficient TDDSs.

Assessment of basic pharmacokinetic parameters of dapagliflozin in TTS formulations in male minipigs

Given the extended time over which diabetes treatment is administered, the transdermal delivery system is anticipated to be a more suitable option for older individuals who may experience difficulty swallowing. The continuous delivery of dapagliflozin and more stable plasma levels are anticipated to reduce the incidence of side effects and the frequency of dosing. The objectives of the study were to determine the safety and plasma pharmacokinetics of dapagliflozin in male minipigs following application of the ointment and skin patch. In the initial phase of the study, the potential for transdermal permeation of dapagliflozin from ointment and transdermal patch to blood plasma of 15 male Göttingen minipigs was investigated. In the subsequent phase, the efficacy of utilising patches of varying strengths and sizes was assessed. The LC/MS method was employed to quantify the concentration of the active substance. The transportation of the studied API to the general circulation and accumulation in tissues were confirmed. The maximum drug concentration (122.99 ng/mL) in plasma was observed on the fourth day of application. The highest calculated Cmax was 131.91 ng/mL with a mean AUC0-last of 6620.7 ng h/mL. Following transdermal administration, dapagliflozin is excreted in the urine. The trend between urinary dapagliflozin 3-O-glucuronide levels and urinary glucose excretion was also observed. The transdermal patch has been demonstrated to be an effective drug delivery system for dapagliflozin.

Role of Natural Polymers in Novel Drug Delivery Systems

Natural polymers have gained significant attention in the field of drug delivery due to their inherent biocompatibility, biodegradability, and low toxicity. This review article aims to provide a comprehensive overview of the diverse roles that natural polymers play in the development of novel drug delivery systems. Beginning with a classification of natural polymers based on their origin (plant, animal, microbial), we explore their unique characteristics and advantages over synthetic counterparts. The review discusses the pivotal role of natural polymers in formulating various drug delivery systems, including sustained/controlled release formulations, targeted delivery platforms, mucoadhesive systems, and nanotechnology-based approaches. Techniques such as emulsification, ionotropic gelation, coacervation, and electrospinning for natural polymer-based drug delivery are elucidated, highlighting their versatility and applicability across different administration routes. Furthermore, we delve into the diverse applications of natural polymers in drug delivery, encompassing oral, transdermal, ocular, injectable, nasal, buccal, and vaginal delivery routes. Recent advances and innovations in combining natural polymers with synthetic counterparts, incorporating stimuli-responsive properties, and personalized medicine approaches are also explored. Despite the numerous advantages offered by natural polymers, challenges such as variability in polymer properties, standardization issues, scale-up challenges, and regulatory considerations are discussed. The review concludes with future perspectives, highlighting emerging trends and opportunities for further research and development in the field of natural polymer-based drug delivery systems. Overall, this review provides valuable insights into the pivotal role of natural polymers in advancing drug delivery technology, paving the way for safer, more efficient, and patient-friendly therapeutic interventions.