AN OVERVIEW: RECENT DEVELOPMENT IN TRANSDERMAL DRUG DELIVERY

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

Nanoemulgel: For Promising Topical and Systemic Delivery

Nanoemulgel delivery system is a fusion of two different delivery systems, wherein the physical state of drug containing nanoemulsion is changed by adding it to the gel matrix, thus enabling more lipophilic drugs to be used in treatment therapies. It solves the major issues such as limiting use of lipophilic drugs, poor oral bioavailability, and unpredictable pharmacokinetic and absorption variations. Simultaneously, its nongreasy nature and easily spreading ability support the patient compliance. Nanoemulgel can be widely used in the treatment of acne, pimple, psoriasis, fungal infection, and inflammation cause by osteoarthritis and rheumatoid arthritis. The delivery of drug via ocular, vaginal, dental, and nose to brain routes for the treatment of diverse local and systemic ailments for instance alopecia, periodontitis, and Parkinson’s are possible. In the cosmetic industries, UV absorber nanoemulgel protected skin from sunburn

Nanoemulsion Based Hydrogel for Enhanced Transdermal Delivery of Ketoprofen

The aim of the present study was to investigate the nanoemulgel as transdermal delivery system for poorly water soluble drug, ketoprofen, in order to overcome the troubles associated with its oral delivery. Different nanoemulsion components (oil, surfactant, and cosurfactant) were selected on the basis of solubility and emulsification ability. Pseudoternary phase diagrams were constructed using titration method to figure out the concentration range of components. Carbomer 940 was added as gel matrix to convert nanoemulsion into nanoemulgel. Drug loaded nanoemulsions and nanoemulgels were characterized for particle size, TEM, viscosity, conductivity, spreadability, rheological behavior, and permeation studies using Wistar rat skin and stability studies. Transdermal permeation of ketoprofen from nanoemulgels was determined by using Franz diffusion cell. Nanoemulgel containing 6% oleic acid as oil, 35% Tween 80, and Transcutol P as surfactant cosurfactant mixture, 56.5% water, 2.5% drug, and 0.6% carbomer was concluded as optimized formulation (NG6). The ex vivo permeation profile of optimized formulation was compared with nanoemulsion and marketed formulation (Fastum). Nanoemulgel showed significantly higher (P&lt;0.05) cumulative amount of drug permeated and flux along with lower lag time and skin retention than marketed formulation. Thus, the study substantiated that nanoemulgel formulation can be used as a feasible alternative to conventional formulations of ketoprofen with advanced permeation characteristics for transdermal application.</jats:p

Improved skin delivery and validation of novel stability-indicating HPLC method for ketoprofen nanoemulsion

Abstract Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID) widely used to treat rheumatoid arthritis and other inflammatory diseases. Normally used by oral route, this drug presents numerous side effects related to this administration route, such as nausea, dyspepsia, diarrhea, constipation and even renal complications. To avoid that, topical administration of ketoprofen represents a good alternative, since this drug has both partition coefficient and aqueous solubility suitable for skin application, compared to other NSAIDs. In this study, we describe the production of a nanoemulsion containing ketoprofen, its skin permeation and in vitro release study and a novel validation method to analyze this drug in the permeation samples and a forced degradation study using skin and nanoemulsion samples. The new HPLC method was validated, with all specifications in accordance with validation parameters and with an easy chromatographic condition. Forced degradation study revealed that ketoprofen is sensitive to acid and basic hydrolysis, developing degradation peaks after exposure to these factors. Concerning in vitro release from the nanoemulsion, release curves presented first order profile and were not similar to each other. After 8 h, 85% of ketoprofen was release from the nanoemulsion matrix while 49% was release from control group. In skin permeation study, nanoemulsion enabled ketoprofen to pass through the skin and enhanced retention in the epidermis and stratum corneum, layer on which the formulation presented statistically different values compared to the control group

Microneedles Assisted Iontophoretic Transdermal Delivery of Drugs

Topical/transdermal delivery offers an attractive alternative to oral and parenteral delivery in terms of non-invasiveness, administration and termination of dose and drug stability etc. However, the excellent barrier system of skin limits the number of drugs that can be delivered in therapeutic quantities to the site of action. Various approaches such as iontophoresis (ITP), microneedles (MN), chemical permeation enhancers, phonophoresis and synthesis of lipophilic analogues have been used to increase drug permeation across skin. ITP and MN have shown promising results in enhancing the topical transdermal delivery. Further, the combination of ITP and MN (ITP+MN) has shown additive or synergistic effects on transdermal drug delivery. The effect of lipophilicity of drug on permeation across skin has been well reported. However, this effect has not been studied under the influence of ITP in microporated skin. Further, the effect of the lipophilicity of delivery vehicle on the transdermal delivery across microporated skin has not been reported. Thus, this dissertation focuses on studying the effect of lipophilicity of drug as well as the delivery vehicle on the skin permeation of drug across microporated skin under the influence of ITP. To investigate the effect of drug’s lipophilicity on its delivery across skin under the influence of ITP and MNs, we selected four model beta blocker drugs, propranolol, acebutolol, atenolol and sotalol, with similar molecular weights and pKa values but varied lipophilicity. The skin permeation of these drugs was studied under the influence of MNs, ITP and their combination across dermatomed human skin. Both ITP and MNs enhanced the skin permeation of hydrophilic as well as lipophilic drugs when used alone. However the combination strategy showed synergistic enhancement for the delivery of hydrophilic drugs. This was attributed to the creation of aqueous channels by MNs that improved the delivery for hydrophilic drugs more than lipophilic drugs. To investigate the effect of lipophilicity/polarity of the delivery vehicle on drug permeation across human skin, we formulated a nanoemulsion using fatty acids of varied lipophilicity, Caproic acid (C6), Caprylic acid (C8), Capric acid (C10) and Lauric acid (C12), for the delivery of a hydrophilic peptide molecule, Proline-Lysine-Valine (KPV). The polarity of the lipids had a significant influence on the delivery of KPV. A parabolic relationship was observed between hydrocarbon chain length and skin permeation rate. Both normal and microporated skin showed similar relationship with the hydrocarbon chain length, indicating that there is no influence of MN on this behavior. Further, the skin retention data of KPv indicated that the deposition of KPV enhanced with the lipophilicity of the fatty acid chain length

Plant Resin Delivery by Nanovectors as an Emerging Approach to Boost Solubility, Permeability and Bioavailability

Resins are complex mixtures of natural constituents containing non-volatile and volatile terpenes, in combination with gums and polyphenols, used since ancient times for their medicinal properties. Current research has evidenced their therapeutic value with a plethora of activities. The main limits of resins and their constituents for their clinical use are low water solubility, poor stability and bioavailability. Therefore, nanovectors including vesicles, solid lipid nanoparticles, micelles, nanoemulsions, microemulsions and mesoporic nanoparticles have been investigated to optimize the biopharmaceutical properties after topical or oral administration of resins or fractions from them, including essential oils or single constituents. In this review, we report the results evidencing that developed nanovectors were able to entrap high amounts of resins or their components, modify the release properties, enhance their cellular uptake and penetration across biological barriers and optimize the biopharmaceutical properties. In addition, the resins or their fractions as enhancer penetration molecules can optimize the architecture and properties of nanovectors in their capacity to circumvent biological barriers. Although no clinical studies have been reported until now, nanovectors represent a huge platform for upgrading therapies and emerging new treatments of resins such as wound healing therapy

FORMULATION AND OPTIMIZATION OF CELECOXIB NANOEMULGEL

Objective: The main objective of this experiment was to prepare and optimized celecoxib nanoemulgel. This formulation can be used for acuterheumatoid arthritis patients.Methods: Celecoxib is a poorly water soluble drug. We prepared celecoxib nanoemulgel to improve intrinsic solubility of celecoxib and enhancedeeper permeation throughout the skin. After several screening, the combination of acetonitrile, triacetin, campul 908P was considered for oil phase;acconon MC8-2EP as surfactant, and capmul MCM C-10 as a co-surfactant accordingly. As per Box-Behnken surface design model, optimization wasdone for all the 13 formulations.Results: Based on pseudo ternary plot, it was found that 4:1 Smix ratio was optimum and possessed maximum drug solubility. Further, screeningshown, 0.25-0.75% carbopol-940 can be a stable candidate for hydrogel preparation. Prepared nanoemulsions and hydrogels were admixed to preparenanoemulgel. Based on overlay plot, EG14* formulation was consider as optimum one, and various evaluation parameters were performed along withother formulations. Using Franz diffusion cell, in-vitro diffusion studies was performed. Almost all the formulations produces good qualitative drugrelease profile. The EG14* shown 95.50% drug release after 12th hrs with standard Higuchi plot (R2 value 0.9989). The optimum viscosity was foundto be 521±0.81 mPas at 100 rpm. The appearance of the formulations was milky, yellowish white with expectable pH ranged from 5.8 to 6.7. Theoptimized formulation has good spreadability coefficient, good ex-vivo diffusion enhancement factor (3.03) as compare to marketed gel. Mostly, ourformulations have less skin irritation and higher anti-inflammatory activity (92.56% of inhibition of paw edema for EG14*).Conclusion: From the thermodynamic studies, it was confirmed that EG14* maintained excellent stability profile in various heating-cooling cycle,centrifugation, and freeze-thaw cycle condition. Hence, it can be conclude that, our formulation, can be consider for pilot scale up

TOPICAL AND SYSTEMIC DERMAL CARRIERS FOR PSORIASIS

Psoriasis is a non-infectious, dry, inflammatory (autoimmune) skin disorder. Treatment approaches include phototherapy, topical, oral and other systemic drug delivery. However, owing to the side effects and incomplete cure accompanying the oral administration as well as phototherapy, the topical route seemed to be more satisfactory for the medical team. Dermal treatment ensuring percutaneous penetration is now highly recommended in topical indications for psoriatic patients, which can be achieved using pharmaceutical carriers. Several carrier systems loaded with antipsoriatic drugs have demonstrated promising results, with some of them strictly being confined to the skin and others allowing for systemic involvement also. The evolution in this area will present a more useful and safer therapy by minimizing the drugs' degradation and loss, and increasing their bioavailability and effectiveness. Since patients require at least three topical applications for almost a 1-year period to gain health benefit, a reduction in the cost of the treatment will be of real value. A distinction of these carriers is made in the current review, to allow the choice of the most suitable pharmaceutical carrier for psoriatic patients requiring either local and/or systemic involvement

INTRANASAL MICROEMULGEL AS SURROGATE CARRIER TO ENHANCE LOW ORAL BIOAVAILABILITY OF SULPIRIDE

Objective: The purpose of this study is to evaluate microemulsion based gel (MBG) of sulpiride "a poorly water soluble antipsychotic with low oral bioavailability."Methods: Gelling polymers such as sodium carboxymethylcellulose (CMC-Na), hydroxyl propyl methyl cellulose (HPMC K4m), carbopol 940 and Na alginate were evaluated for their potential to gel sulpiride microemulsions (MEs) without affecting the MEs structure. Also, sulpiride solution (SS) and conventional gel (without ME) were prepared and compared with MBG. Gel formulations were checked for their viscosity, pH, spreadability (S), mucoadhesive force (MF), and nasal ciliotoxicity studies. The in vitro release of sulpiride across a cellophane membrane and its permeation through the nasal mucosa in phosphate buffered saline pH 6.8 (PBS) were also performed. In addition, a pharmacodynamic study of optimized formulae compared to SS and microemulsion (ME) was evaluated in rats.Results: CMC-Na and HPMC K4m were not able to gel sulpiride loaded MEs while Na alginate gave an unclear gel with a sticky texture. Results revealed that the viscosity, mucoadhesion force, and spreadability of the MBG increased with increasing carbopol 940 concentrations. The flux was arranged as the following, MBG&gt;conventional gel&gt;sulpiride solution (SS). According to histopathological study, safe and non-irritant MBGs suitable for nasal administration were successfully prepared. Finally, the pharmacodynamic study indicated that intranasal sulpiride MBG had a significant effect (*P&lt;0.001) than SS and ME administered either intravenous or intranasal.Conclusion: MBG provides signiï¬cant enhancement in nasal bioavailability not only by absorption enhancing effect of ME but also, by increasing nasal residence tim