Development Of Transdermal Delivery System Research Articles

Methodology of the Development of a Topical Transdermal Fucoidan Delivery System

Introduction. Marine-derived polysaccharides are promising candidates for the development of innovative drugs. One of such compounds is the polysaccharide fucoidan from brown seaweeds, which shows anticoagulant and anti-inflammatory activity. The development of topical transdermal formulation for the treatment of chronic venous diseases is of particular interest, because with targeted delivery, the active compound in high concentration comes directly to the site where the drug is required, while the risk of side effects is minimal.Aim. Experimental and theoretical justification of the methodological scheme for the development of a transdermal delivery system with fucoidan for local therapy using the Quality by Design (QbD) approach.Materials and methods. Fucoidan was isolated from the thalli of Fucus vesiculosus L. from the Barents Sea according to the original technology of the MMBI RAS. All excipients were approved for medical use. The experiments for rational selection of the excipients for the transdermal delivery system (TSD) were planned using the Greek-Latin square 4 × 4 with repeated observations. The colloidal and thermal stability and pH were evaluated as physicochemical parameters of TSD Structural and mechanical properties of TSD were deter-mined with rotational viscometer. The dissolution rate of fucoidan in vitro was evaluated using the paddle-over-disk method at a temperature of 32 ± 0.5 °C.Results and discussion. The composition and technology of topical TSD цwith fucoidan were developed using the QbD concept. The composition and technology of topical TSD with 15 % of fucoidan as active ingredient were developed. TSD has thermo- and colloidal stability, and has a pH value close to the pH of human skin. Poloxamer 407 was used as a gel base; olive oil was used as a hydrophobic phase. It was found that the ratio of poloxamer 407 to the aqueous phase should be no less than 0.1 and no more than 0.37; the ratio of water to the aqueous phase should not be less than 0.56 and not more than 0.69; and the ratio of polyoxyl 40 hydrogenated castor oil to the oil phase must be at least 0.34. It was found that 9 % poloxamer 407 provides the necessary structural and mechanical properties of TSD. It has been established that the developed TSD of fucoidan with poloxamer 407 belongs to non-Newtonian flow types with plastic properties and has thixotropy.Conclusion. The complex of studies based on QbD approach led to the experimental and theoretical justification of the methodological scheme for the development of a transdermal delivery system with marine polysaccharide fucoidan. The methodological scheme takes into account the physicochemical and technological features of fucoidan and allows you to create a high-quality TSD that ensures stability and complete release of the active substance.

Microneedle-assisted transdermal delivery of amlodipine besylate loaded nanoparticles

Transdermal drug delivery has been developed to increase drug bioavailability and improve patient compliance. The current study was carried out to formulate and evaluate a transdermal delivery system loaded with biodegradable polymeric nanoparticles for sustained delivery of amlodipine besylate (AMB). For this purpose, AMB was incorporated into CS nanoparticles that were prepared via the ionic gelation method. Three formulations containing different blends of CS and tripolyphosphate were investigated for the preparation of the nanoparticles and evaluated for particle size (PS), zeta potential (ZP), loading capacity (LC), encapsulation efficiency (EE), scanning electron microscope (SEM), and drug release kinetics. The smallest observed particle size was 321.14 ± 7.21 nm (NP-3). Across all formulations, the highest observed EE% was 87.2 ± 0.12% (NP-2), and the highest observed LC% was 60.98 ± 0.08% (NP-2). Microneedles were formed by using 15% polyvinylalcohol (PVA) (F1), 15% PVA with 1% propylene glycol (PG) (F2), and 15% PVA with 5% PG (F3). On investigating drug release rates, it was observed that drug permeation and steady-state flux (Jss) both increased proportionally with increasing PG concentration. Nanomedicine, when combined with physical techniques, has opened new opportunities for the growth and development of transdermal delivery systems in the pharmaceutical industry. In conclusion, biodegradable polymeric nanoparticles loaded in hydrogel microneedles served as a potential system for the transdermal delivery of AMB in a controlled manner

Preparation and characterization of sumatriptan loaded solid lipid nanoparticles for transdermal delivery

Over the past decade, there has been great attention paid to the development of transdermal delivery systems for sumatriptan, the most commonly prescribed drug for the treatment of migraine headaches. Given the various gastrointestinal side effects of sumatriptan in oral administration and low bioavailability in nasal dosage forms, focus has been on transdermal delivery. The main purpose of this study was to prepare and assess a transdermal formulation of sumatriptan, based on solid lipid nanoparticles (SLNs), to eliminate the undesirable side effects and also improve its percutaneous permeation rate. Topical gel of sumatriptan loaded SLNs was also formulated with respective characteristics assessed. Sumatriptan loaded SLNs were prepared using solvent diffusion/evaporation method. Particle size, entrapment efficiency, in vitro release study and skin permeation analysis of sumatriptan were performed to characterize the prepared SLNs. Then, sumatriptan loaded SLNs were incorporated in a gel formulation as a topical delivery system to assess the percutaneous permeation of sumatriptan. Different compositional and technical variables were considered to optimize the formulation using the design of experiment and drug release performance from the best SLN formulation was evaluated. The results indicated that sumatriptan loaded SLN formulation exhibited increased skin permeation of the drug relative to sumatriptan conventional gel formulation.

Penghantaran Obat Anti-Inflamasi Non-Steroid (NSAID) Melalui Rute Transdermal

The transdermal route has several advantages compared to the per-oral route, such as the limitations of the First Pass Effect (FPE). However, the development of Transdermal delivery systems is challenging because of the barrier provided by the skin. NSAIDs are medicines that have been used in chronic conditions and potentially causing severe gastrointestinal adverse effects. The combinations of nanoparticle and iontophoresis in transdermal delivery of NSAID will be beneficial for the future use.

DEVELOPMENT AND CHARACTERIZATION OF TRANSDERMAL DELIVERY SYSTEM OF DOXAZOSIN MESYLATE

Objective: The study involved development of transdermal delivery system (TDDS) of doxazosinmesylate (doxa) to achieve effective systemic delivery of the drug.Methods: TDDS of doxa was prepared using hydroxypropyl methyl cellulose (HPMC) K100LV and polyvinyl pyrrolidone (PVP) K30 in 3:1 ratio solvent casting method. The formulation was evaluated for folding endurance, moisture uptake, pH, drug content and in vitro permeation. Various permeation enhancers were incorporated at 5% w/w concentration into the patch formulationto study their impact on the drug permeation. The TDDS made with Transcutol® as an enhancer was subjected to accelerated stability studies and in vivo skin irritation studies.Results: The developed TDDS showed folding endurance of 170, moisture uptakeof 15.7%, pH of 6.3, and drug content of 99±1.1% and 66% in vitro permeation of doxa over 24h. The effect of various enhancers expressed in terms of average flux can be summarized as Transcutol® (10.6±2.1 µg/cm2h)>dimethyl sulfoxide(10.17±1.2 µg/cm2h)>benzyl alcohol (9.55±1.3 µg/cm2h)>no enhancer (8.86±1.1 µg/cm2h)>dimethyl isosorbide (8.21±1.5 µg/cm2h)>Isostearic acid (7.82±1.4 µg/cm2h)>propylene carbonate (7.67±1.4 µg/cm2h)>oleic acid (7.12 µg±0.8/cm2h). The formulation was found to be stable during the accelerated stability studies. In vivo studies indicated absence of skin irritation effect the TDDS containing Transcutol®.Conclusion: TDDS of doxa comprising HPMC K100LV and PVPK30 in the ratio of 3:1 and 5% Transcutol® could serve as a potential TDDS in the treatment of benign prostatic hyperplasia (BPH) and hypertension.

Development of Transdermal Delivery System of Vildagliptin and Its Comparison with Oral Therapy.

Purpose: The long term oral therapy of vildagliptin is associated with potential hepatotoxicity and low patient compliance. This study aims at development of a drug in adhesive transdermal patch system of vildagliptin using pressure sensitive acrylic polymers and compare the pharmacokinetics with oral therapy. Methods: The prospective of different chemical enhancers in improving the transport of vildagliptin was assessed ex vivo. In vivo permeation studies in rats were performed using patch system contain sodium lauryl sulfate as enhancer. Results: Drug solubility varied among adhesive bases tested and maximum value (15% w/w) observed with Duro-Tak 87-2510. Incorporation of chemical agents significantly improved the permeation of vildagliptin, but not to the same extent. The highest flux value of vildagliptin was obtained by the addition of sodium lauryl sulfate (22.96 ± 3.58 μg/cm2/h; P<0.0001), which is ~4 folds higher as compared to control. Pharmacokinetic profiles of vildagliptin were different for transdermal and oral delivery with significantly high bioavailability by transdermal delivery. The AUC0-α in transdermal delivery (1018.43 ± 79.56 ng.h/mL) was ~14 folds higher (P<0.0001) as compared to oral administration. Conclusion: The current study concludes that the fabricated drug in adhesive transdermal system could be employed for the effective delivery of vildagliptin.

Recent advances in the development of transdermal delivery systems for treatment of infertility

Recent advances in the development of transdermal delivery systems for treatment of infertility

Skin regenerative potentials of curcumin

Curcumin, an active constituent of the spice turmeric, is well known for its chemopreventive properties and is found to be beneficial in treating various disorders including skin diseases. Curcumin protects skin by quenching free radicals and reducing inflammation through the inhibition of nuclear factor-kappa B. Curcumin also affects other signaling pathways including transforming growth factor-β and mitogen-activated protein kinase pathway. Curcumin also modulates the phase II detoxification enzymes which are crucial in detoxification reactions and for protection against oxidative stress. In the present review, the biological mechanisms of the chemopreventive potential of curcumin in various skin diseases like psoriasis, vitiligo, and melanoma is discussed. The application of curcumin in skin regeneration and wound healing is also elucidated. We also explored the recent innovations and advances involved in the development of transdermal delivery systems to enhance the bioavailability of curcumin, particularly in the skin. Recent clinical trials pertaining to the use of curcumin in skin diseases establishes its benefits and also the need for additional clinical trials in other diseases are discussed.

Natural Oils as Skin Permeation Enhancers for Transdermal Delivery of Olanzapine: In Vitro and In Vivo Evaluation

The feasibility of development of transdermal delivery system of olanzapine utilizing natural oils as permeation enhancers was investigated. Penetration enhancing potential of corn (maize) oil, groundnut oil and jojoba oil on in vitro permeation of olanzapine across rat skin was studied. The magnitude of flux enhancement factor with corn oil, groundnut oil and jojoba oil was 7.06, 5.31 and 1.9 respectively at 5mg/ml concentration in solvent system. On the basis of in vitro permeation studies, eudragit based matrix type transdermal patches of olanzapine were fabricated using optimized concentrations of natural oils as permeation enhancers. All transdermal patches were found to be uniform with respect to physical characteristics. The interaction studies carried out by comparing the results of ultraviolet, HPLC and FTIR analyses for the pure drug, polymers and mixture of drug and polymers indicated no chemical interaction between the drug and excipients. Corn oil containing unsaturated fatty acids was found to be promising natural permeation enhancer for transdermal delivery of olanzapine with greatest cumulative amount of drug permeated (1010.68 μg/cm²/h) up to 24 h and caused no skin irritation. The fabricated transdermal patches were found to be stable. The pharmacokinetic characteristics of the final optimized matrix patch (T2) were determined after transdermal application to rabbits. The calculated relative bioavailability of TDDS was 113.6 % as compared to oral administration of olanzapine. The therapeutic effectiveness of optimized transdermal system was confirmed by tranquillizing activity in rotarod and grip mice model.

Innovations in Transdermal Drug Delivery System - A Review

The number of medications and the ways in which they can be administered have expanded dramatically over the years. One such advance has been the development of transdermal delivery systems. 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 delivery of the drug molecules to the systemic circulation via this route. Various types of transdermal approaches used to incorporate the active ingredients include use of prodrugs/lipophilic analogs, permeation enhancers, sub saturated systems and entrapment into vesicular systems. Innovations in technologies continue to occur at a positive rate, making the technology a fertile and vibrant. This article deals with the innovations in the field of TDDS to improve the release rate and other parameters and most suitable to the patient.

Use of Chitosan Membranes to Mimic Human Epidermis for the Development of an Estradiol Delivery System

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.

Development and Evaluation of Ethyl Cellulose-Based Transdermal Films of Furosemide for Improved In Vitro Skin Permeation

Transdermal films of the furosemide were developed employing ethyl cellulose and hydroxypropyl methylcellulose as film formers. The effect of binary mixture of polymers and penetration enhancers on physicochemical parameters including thickness, moisture content, moisture uptake, drug content, drug-polymer interaction, and in vitro permeation was evaluated. In vitro permeation study was conducted using human cadaver skin as penetration barrier in modified Keshary-Chein diffusion cell. In vitro skin permeation study showed that binary mixture, ethyl cellulose (EC)/hydroxypropyl methylcellulose (HPMC), at 8.5:1.5 ratio provided highest flux and also penetration enhancers further enhanced the permeation of drug, while propylene glycol showing higher enhancing effect compared to dimethyl sulfoxide and isopropyl myristate. Different kinetic models, used to interpret the release kinetics and mechanism, indicated that release from all formulations followed apparent zero-order kinetics and non-Fickian diffusion transport except formulation without HPMC which followed Fickian diffusion transport. Stability studies conducted as per International Conference on Harmonization guidelines did not show any degradation of drug. Based on the above observations, it can be reasonably concluded that blend of EC-HPMC polymers and propylene glycol are better suited for the development of transdermal delivery system of furosemide.

Transdermal Delivery of Tadalafil. I. Effect of Vehicles on Skin Permeation

Transdermal delivery that avoids the presystemic disposition can provide an alternative to oral administration of tadalafil. Accordingly, the aim of this study was to select the best vehicle as the first step in optimization of tadalafil transdermal delivery. The vehicles were used neat or in selected binary combinations and were evaluated for drug solubilization and transdermal delivery. The drug solubility in pure vehicles were ranked as polyethylene glycol (PEG) 400 > propylene glycol (PG) > ethanol > ethyl oleate (EO) > isopropyl myristate (IPM) > water. The solubility in binary systems containing ethanol at 2:1 ratios with EO or IPM was greater than that obtained with pure ethanol, EO, or IPM. This effect could be due to the cosolvency effect. The transdermal drug delivery from pure vehicles was ranked as IPM > EO > ethanol > PG > PEG > water. The delivery from binary mixtures of ethanol with either IPM or EO was higher than that obtained from pure solvents with the delivery increasing with increasing ethanol concentration in the mixtures. The delivery from binary mixtures was synergistic rather than additive. The study thus demonstrated a potential of tadalafil transdermal delivery. Binary combinations of ethanol with either IPM or EO provided the first step forward toward the development of transdermal delivery system for tadalafil.

Transdermal delivery by iontophoresis

Recently there has been an increased interest in using iontophoretic technique for the transdermal delivery of medications, both ionic and nonionic. This article is an overview of the history of iontophoresis and factors affecting iontophoretic drug transfer for the systemic effects and laws for development of Transdermal delivery system are discussed.

Measuring Adhesive Performance in Transdermal Delivery Systems

The therapeutic performance of a transdermal delivery system (TDS) can be affected by the quality of contact between the patch and the skin. The adhesion of a TDS to the skin is obtained by using pressure-sensitive adhesives (PSAs), which are defined as adhesives capable of bonding to surfaces with the application of light pressure. The adhesive properties of a TDS can only be fully and correctly characterized by considering the following factors: (i) the property that enables an adhesive to form a bond with the surface of another material upon brief contact and under light pressure (tack); (ii) the resistance of the matrix to flow that could be considered as an expression of the cohesiveness of the matrix itself (creep resistance); and (iii) the force required to peel away a patch from a surface (peel adhesion). In this paper, attention is focused on the most widely used methods for the measurement of TDS adhesive properties in development studies and in the quality control of TDSs. The most critical formulative variables in the development of TDSs are the type and concentration of additives used, the drug loaded, the PSA thickness, the composition and thickness of the backing layer, and the solvent residue. There is a lack of evidence for a relationship between the results obtained in in vitro adhesion tests and the in vivo adhesion performance of TDSs. Therefore, an analysis of the percentage of TDSs that lifted and/or detached during pharmacokinetic and clinical studies should be performed during development studies. No official tests for adhesive strength are currently included in the TDS monographs of the most authoritative pharmacopeias. At present, the medical application of TDS relies on tests standardized by the adhesive tape industry or prescribed in the adhesive tape monographs of US and Japanese Pharmacopoeias, or adaptations of these. The development of new methods is recommended to meet the specific requirements of evaluating TDSs, and to improve the correlation between in vitro tests and in vivo performance.

Structure-activity relationship of chemical penetration enhancers in transdermal drug delivery.

Transdermal drug delivery (TDD) is the administration of therapeutic agents through intact skin for systemic effect. TDD offers several advantages over the conventional dosage forms such as tablets, capsules and injections. Currently there are about eight drugs marketed as transdermal patches. Examples of such products include nitroglycerin (angina pectoris), clonidine (hypertension), scopolamine (motion sickness), nicotine (smoking cessation), fentanil (pain) and estradiol (estrogen deficiency). Since skin is an excellent barrier for drug transport, only potent drugs with appropriate physicochemical properties (low molecular weight, adequate solubility in aqueous and non-aqueous solvents, etc) are suitable candidates for transdermal delivery. Penetration enhancement technology is a challenging development that would increase significantly the number of drugs available for transdermal administration. The permeation of drugs through skin can be enhanced by physical methods such as iontophoresis (application of low level electric current) and phonophoresis (use of ultra sound energy) and by chemical penetration enhancers (CPE). In this review, we have discussed about the CPE which have been investigated for TDD. CPE are compounds that enhance the permeation of drugs across the skin. The CPE increase skin permeability by reversibly altering the physicochemical nature of the stratum corneum, the outer most layer of skin, to reduce its diffusional resistance. These compounds increase skin permeability also by increasing the partition coefficient of the drug into the skin and by increasing the thermodynamic activity of the drug in the vehicle. This review compiles the various CPE used for the enhancement of TDD, the mechanism of action of different chemical enhancers and the structure-activity relationship of selected and extensively studied enhancers such as fatty acids, fatty alcohols and terpenes. Based on the chemical structure of penetration enhancers (such as chain length, polarity, level of unsaturation and presence of some special groups such as ketones), the interaction between the stratum corneum and penetration enhancers may vary which will result in significant differences in penetration enhancement. Our review also discusses the various factors to be considered in the selection of an appropriate penetration enhancer for the development of transdermal delivery systems.

Transdermal drug delivery: useful paradigms.

The successful development of transdermal delivery systems requires a systematic evaluation and understanding of a number of complex phenomena. For example, the study of drug transport through skin (and other biomembranes) has lead to a significant advance in our ability to select drugs which are appropriate for transdermal delivery. Drug release from the transdermal system is also crucial to effective drug delivery and provides a clear opportunity for research in adhesion, polymer physical chemistry, mass transport, and film coating, to name a few. The incorporation of several disciplines into transdermal science holds the exciting promise to provide rapid advances in this technology.

Transdermal delivery of levonorgestrel

This review of the research and development of transdermal delivery systems for levonorgestrel and combinations of levonorgestrel and estrogens also contains explanatory material on skin structure and absorption of drugs by diffusion and partition, permeability and use of enhancers to facilitate absorption, use of pro-drugs and derivatives, and cutaneous side effects. Drug absorption entails diffusion through the lipophilic stratum corneum and the hydrophilic epidermis, and between the two layers. Diffusion of levonorgestrel is driven by the saturated solution in the medium, such as ethanol, but the rate was insufficient. The target delivery rate for levonorgestrel used alone as a contraceptive is 35 mcg/day for transdermal use, which would require a delivery rate of 0.3 mcg/sq.cm. Ethyl acetate was found to be the best "penetration enhancer," speeding absorption 17-fold in rat skin. Levonorgestrel in ethyl acetate diffused through human cadaver skin at a rate requiring a patch of 7.5 sq. cm. Use of pro-drugs and derivatives is based on the theory that even though the derivative may diffuse more slowly because of its larger size, it is more soluble in both lipophilic and hydrophilic media. The best pro-drug was levonorgestrel-glycidol, with a 32-fold increase in penetration. Pro-drugs have the drawback of requiring complete FDA approval. They are hydrolyzed in skin to the native steroid, however. The type of transdermal delivery system needed for levonorgestrel is a membrane-based patch with a reservoir. Ethylene vinyl acetate copolymer systems have been tested or rabbits and in Phase I clinical trials. The micro-reservoir systems has been marketed for estradiol in a 3.5-day patch. A similar system has been developed experimentally using levonorgestrel and estradiol combined. Most transdermal systems cause mild skin irritation in a high proportion of users, but the likelihood of contact allergy or urticaria with levonorgestrel is minimal. Development of a transderm system with levonorgestrel and ethyl acetate, which is generally recognized as safe (GRAS), would be feasible as soon as the stability of levonorgestrel in ethyl acetate is defined.

Skin immunology: The Achilles heel to transdermal drug delivery

There are numerous advantages associated with the development of transdermal delivery systems for pharmacologically active drugs and chemicals. Before the potential of transdermal drug delivery can be fully realized, however, researchers are being forced to cope with the problems associated with the development of allergic contact dermatitis and other types of immune responses that can emerge in individuals receiving this form of therapy. This appears to be a unique problem of the transdermal delivery systems since the same agents, given orally or by injection, are accepted by the body without immunological incident. The development of an immune response to a trans dermally delivered drug could have serious implications. It is conceivable that in addition to the immediate problem of allergic contact dermatitis, an immune response could develop that could neutralize the drug's activity. As a result, the sensitized patient may no longer derive any clinical benefit from its usage or that of chemically related compounds. The reasons why and how such skin-associated immune responses are induced, as well as an overview of the skin as an immunologically important organ system, will represent the major focus of this presentation.