Formulation For Transdermal Delivery Research Articles

Predicting skin permeation-enhancing effect of fixed oils using saturated to unsaturated fatty acid ratio content

Background: Transdermal drug delivery is non-invasive and advantageous as it improves patient compliance.
 Objective: This study evaluated the effect of varying ratios of saturated to unsaturated fatty acids in fixed oils on the permeation of ibuprofen across pig dorsal skin.
 Methods: The solubility of ibuprofen in soybean oil, theobroma oil, and shea butter (fixed oils) was evaluated and in vitro skin permeation studies were conducted using Franz diffusion cells.
 Results: A significant difference in permeability parameters, such as flux and effective skin permeability, in the different formulations was observed. Skin permeation depended on the ratio of saturated to unsaturated fatty acids. It also depended on the type and concentration of individual saturated and unsaturated fatty acids present in the fixed oils. The skin permeation of ibuprofen increased with an increasing ratio of palmitic acid (PA) to oleic acid (OA) concentrations. The highest flux was obtained in the theobroma oil formulation, with a PA:OA ratio of 0.78. The lowest flux was obtained in the shea butter formulation, with a PA:OA ratio of 0.09. The PA:OA ratio was 0.46 in the soybean oil formulation.
 Conclusion: These results suggest that the ratio of saturated to unsaturated fatty acids in fixed oils could be used as a model for predicting the rate of skin permeation of drugs in oil-based formulations. Depending on the desired rate of drug permeation, different combinations of the ratio of saturated to unsaturated fatty acids can be used in formulations for transdermal delivery.

Acanthus mollis Formulations for Transdermal Delivery: From Hydrogels to Emulsions.

Topical formulations of Acanthus mollis L. leaf and the optimization of the release of their active compounds and their topical bioavailability were investigated for the first time. In vitro, the release of active compounds from three formulations-an oil-in-water cream and two hydrogels (Carbopol 940 and Pluronic F-127)-was determined using Franz diffusion cells. Detection and quantification of the compounds was performed via high-performance liquid chromatography with a photodiode array (HPLC-PDA). DIBOA, a bioactive compound of this medicinal plant, exhibited release kinetics of the Weibull model for the Carbopol and Pluronic F-127 formulation, identifying it as a potential active agent to optimize the topical distribution of the formulations. The implications extend to applications in inflammation treatment and tyrosinase inhibition, suggesting that it can make a significant contribution to addressing skin conditions, including melanoma and various inflammatory diseases.

Comparative pharmacokinetic studies of transferosomes loaded gel and pressure sensitive adhesive based patch formulation for transdermal delivery of benztropine mesylate

Oral bioavailability of benztropine mesylate (BZM) is low due to its limited gastric absorption, low biological half-life, and susceptibility to extensive hepatic first pass metabolism. It is an anti-muscarinic drug used for the management of Parkinson's disease. The goal of the present research work was to compare a BZM transferosome-loaded Carbopol 940 gel formulation and an acrylate pressure sensitive adhesive based transdermal patch for their efficacy in transdermal penetration and pharmacokinetic profiles. BZM transferosomes were formulated using the thin-film hydration method. The developed formulation showed a (-) 12.0 mV zeta potential and a mean vesicle size of 138.5 nm. When compared to aqueous BZM solution, transferosomes exhibited a considerable increase in transdermal penetration in an ex vivo study across isolated rat skin. When compared to oral, intravenous, and drug-in-adhesive transdermal patch, in vivo pharmacokinetic investigations in Wistar rats revealed an increase in AUC, Tmax, and MRT and a higher and prolonged drug release from transferosome-loaded gel formulations. The findings suggest that the BZM transferosome-loaded gel might be a better and more patient-friendly alternative to oral administration of BZM for the management of Parkinson's disease.

Freeze-Dried Camelina Lipid Droplets Loaded with Human Basic Fibroblast Growth Factor-2 Formulation for Transdermal Delivery: Breaking through the Cuticle Barrier to Accelerate Deep Second-Degree Burn Healing.

Transdermal administration of chemo therapeutics into burn healing may be an effective treatment to reduce toxic side effects and improve patient compliance for burns. As a transdermal delivery system, Camelina lipid droplets (CLDs) have received great attention due to their biocompatibility, high drug payload, and rapid absorption. However, the absorbed-related mechanisms of Camelina lipid droplets have not yet been reported. Thus, this paper not only demonstrated that CLD can accelerate skin burn healing through promoting hFGF2 absorption, but also elucidated the mechanism between the skin tissue and keratinocytes using Franz, HE staining, DSC, FTIR spectroscopy, and atomic force microscopy with the presence of CLD-hFGF2 freeze-dried powder. We found that the cumulative release rate of CLD-hFGF2 freeze-dried powder was significantly higher than that of free hFGF2 freeze-dried powder into the skin. At the same time, CLD can change the structure and content of lipids and keratin to increase the permeability of hFGF2 freeze-dried powder in skin tissue. Unlike the free state of hFGF2, the biophysical properties of single cells, including height and adhesion force, were changed under CLD-hFGF2 freeze-dried powder treatment. Meanwhile, CLD-hFGF2 freeze-dried powder was more easily taken up through keratinocytes without damaging cell integrity, which provided a new viewpoint for understanding the absorption mechanism with the CLD system for cellular physiology characteristics. Overall, our findings demonstrated that CLD could break through the stratum corneum (SC) barrier and elucidated the transport mechanism of lipid droplets in skin tissue, which provides a crucial guideline in drug delivery applications for future engineering.

Formulation and Characterization of Novel Transfersomes Gel for Enhance TDDS of Losartan Potassium

A transferosome is the first generation of an elastic liposome prepared from phospholipids and edge activators. An edge activator is often a single-chain surfactant with a high radius of curvature that destabilizes the lipid bilayers of vesicles and increases the deformability of the bilayers, thereby making the vehicle ultra-deformable. Losartan potassium is an orally active angiotensin-II receptor antagonist used in the treatment of hypertension due to mainly blockade of AT1 receptor. It is freely soluble in water, slightly soluble in acetonitrile, and soluble in isopropyl alcohol. The aim of the present study was to investigate the potential of transfersomal gel formulations for transdermal delivery of losartan potassium by reverse phase evaporation method. Characterization of transfersomes gel performed by vesicle size, pH measurements, drug content, entrapment efficiency, in vitro drug diffusion study, spreadability and stability study. In the formulations pH is found to be around 6.8 to 6.9, pH is found in the range of 6 which is compatible with skin. In the formulations spreadability is found to be around 6.75 to 10.11 g m cm/sec. The prepared gel containing losartan potassium-loaded transfersomal formulation was optimized and can be use for topical preparation. The results were obtained which showed that transfersomal gel was a promising candidate for transdermal delivery with targeted and prolonged release of a drug. It also enhances skin permeation of many drugs.
 Keywords: Transferosome gel, Losartan potassium, Antihypertensives, Reverse phase evaporation method

Pharmaceutical development of metronidazole loaded transferosome gel for skin delivery

Objective: The focus of this research was out whether a transfersomal gel formulation for transdermal delivery of Metronidazole. Methods: Azole Antifungals include metronidazole, which is used to treat fungal and yeast infections. Transferosomes are supra-molecular aggregates that are ultra-flexible and have a high ability to penetrate mammalian skin intact. Drug encapsulation in various transfersomal formulations containing various ratios of different drug concentrations (0.05, 0.1, 0.2, 0.3, 0.4, 0.5 g) and Carbopol-934 (0.5, 1, 2 g) is being researched for use as a transferosomal gel.Results: Entrapment efficiency (EE %), drug content, in-vitro skin permeation tests, and stability investigations were performed on the produced formulations. The vesicles were spherical in shape, as confirmed by Transmission Electron Microscopy. Metronidazole was successfully pinned with a standardised drug content in all formulations, according to the resultsThe 0.1 g Metronidazole optimised transferosome formulation MG2 showed promising results, with maximum drug release (94.32%) and maximum drug release (94.32%). Conclusion: According to this report, transferosomes are a promising long-term delivery mechanism for metronidazole and have reasonably good stability.This study suggests that transferosomes containing Metronidazole may be used as a transdermal drug delivery tool for fungal skin infections.

Simvastatin-Loaded Lipid Emulsion Nanoparticles: Characterizations and Applications.

Simvastatin (SIM) is a diet drug to treat high lipid levels in the blood. It has the drawback of being metabolized in humans’ gastrointestinal tract (GIT) when taken in an oral dosage form. To enhance the role of SIM in treating hyperlipidemias and bypassing its metabolism in GIT, a biodegradable nanocarrier as a SIM-loaded lipid emulsion nanoparticle via the solvent injection method was designed. Cholesterol acts as a lipid core, and Tween 80 was utilized to stabilize the core. The optimized nanoformulation was characterized for its particle diameter, zeta potential, surface morphology, entrapment efficiency, crystallinity, and molecular interaction. Furthermore, the transdermal hydrogel was characterized by physical appearance, rheology, pH, and spreadability. In vitro assays were executed to gauge the potential of LENPs and olive oil for transdermal delivery. The mean particle size and zeta potential of the optimized nanoparticles were 174 nm and −22.5 mV 0.127, respectively. Crystallinity studies and Fourier transform infrared analyses revealed no molecular interactions. Hydrogels showed a sustained release compared to SIM-loaded LENPs that can be proposed as a better delivery system for SIM. We encourage further investigations to explore the effect of reported formulations for transdermal delivery by in vivo experiments.

Formulation Development and Evaluation of Transfero-somes Nano Gel Loaded with Levocetirizine Transfero-somes

A new drug delivery technology called transferosomes were came into existence which is an artificial vesicle designed to show the characteristics of a cell vesicle suitable for controlled and potentially directed drug delivery. Transferosome is a highly flexible and stress- responsive compound, complex compound and highly deformed vesicle with an aqueous core surrounded by the complex lipid bilayer thus enabling it to deliver both hydrophilic and hydrophobic drug. Urticaria is a general condition distinguished as brief erythematous and oedematous plaques or papules with defined erythematous borders and central clearing, identified as hives/wheals. Levocetirizine which is used for the treatment is a H1 anti histamine that is actively used in treatment of urticaria. The aim of the present research work was to investigate the potential of transferosome formulations for transdermal delivery of levocetirizine. The transferosomes were formulated by lipid film hydration technique using Rotary vacuum Evaporator. In the present work levocetirizine vesicle was efficaciously formulated using an appropriate ratio of tween 80 and soya lecithin and was incorporated into gel since gel formulations are easy to administer and patient compliance. Levocetirizine transferosomes was evaluated for vesicle characteristicslike zeta potential, poly-dispersibility index, TEM, and stability study. Theaverage sizes of transferosome were found to be 566.6nm and poly dispersity index (PI) was found to be 0.532, zeta potential of the transferosome was found to be -2.3 mV which indicates that transferosome formulation is stable. Levocetirizine gel was prepared by using various concentrations of Carbopol 934 and is evaluated for their gel characteristics like pH, viscosity, Spreadability, extrudability, homogeneity, drug content, diffusion etc. Gel containing 2% Carbopol show best and promising results. Levocetirizine transferosomal gel were efficaciously formulated by utilizing levocetirizine transferosome which was prepared by thin film hydration method by using soya lecithin and tween 80 in the ratio 85:15. Other Oral formulation used in treatment for urticaria have disadvantage like poor bioavailability, 1st pass metabolism, patient non-compliance etc. Transferosome nano gel loaded with levocetirizine transferosome was found to be more effective than other oral formulations used in treatment for urticaria since transferosome are capable of passing through lipid layer and delivering drug into systemic circulation with maximum bioavailability.

Enhancement of Transdermal Permeation of Indinavir Sulfate via EthosomeVesicles

The aim of the present study is to investigate the potential of ethosomal formulations for transdermal delivery of indinavir sulphate from ethosomes. Vesicles containing phosphatidylcholine mixed with ethanol and indinavir sulphate were prepared by conventional mechanical stirrer method and characterized by various parameters (vesicles shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, turbidity and in vitro drug release). The effect of different formulation variable on skin permeation of indinavir sulphate was studied via synthetic semipermeable membrane or skin of new born mice by using diffusion cell. The selected system were incorporated into carbopol 934P gel and evaluated for both drug permeation and mice skin deposition. The optimized ethosomal formulation showed transdermal flux of 25.01±0.34 μg/cm2 /h across rat skin as compared to 2.98±0.21μg/cm2 /h for plane drug solution, 4.28±0.54 μg/cm2 /h for hydroethanolic solution and 9.7±0/21 μg/cm2 /h for classical liposomes. The obtained flux was nearly 7.5 and 12.04 times higher than conventional liposomal formulation bearing indinavir sulphate and plain drug solution. These results suggest that ethosomes are potential vehicles for improved transdermal delivery of indinavir sulphate.

Microemulsion and microemulsion gel formulation for transdermal delivery of rutin: Optimization, in-vitro/ex-vivo evaluation and SPF determination

In this research work, the designation of a new microemulsion formulation for the transdermal application of rutin was investigated. After the construction of pseudo-ternary phase diagrams containing tween 80 as a surfactant, ethylene glycol as co-surfactant and IPM (Isopropyl myristate) as the oil phase, the D-optimal mixture experimental design was used for the optimization process. The independent variables were oil, surfactant/co-surfactant and water weight concentrations and the two response variables were rutin solubility in microemulsions and drug release from microemulsions. After that, physicochemical characterization and stability studies were performed. In the other part the rutin, as an active pharmaceutics agent was loaded in the optimized microemulsion formulation to study kinetic of its release and sun protection factor. To investigate the ex-vivo skin permeation and retention of the drug from the carriers, the optimized formulation and its gel form, were examined on rat skin at similar conditions. The proposed formulation showed different release rate, skin permeation, sun protection factor and particle size, compared to recent works. Obtained results indicated that the microemulsion formulation can be used, especially in gel form, as an effective vehicle for prolong transdermal delivery of rutin desirably in sunscreen formulations.

Transfersomes- a Novel Vesicular Carrier for Enhanced Transdermal Delivery of Stavudine: Development, Characterization and Performance Evaluation

The aim of the present study was to investigate the potential of transfersomal formulations for transdermal delivery of Stavudine and to evaluate Span 80, Tween 80, Sodium cholate and Sodium deoxycholate as edge activators. Vesicles containing phosphatidylcholine (PC) mixed with edge activators and Stavudine were prepared by conventional rotary evaporation method and characterized by various parameters (vesicles shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, turbidity and in vitro drug release). The compositions of refined formulations were predicted, liposomes prepared and tested against control. Skin permeation profile of transfersomal formulation bearing Stavudine was observed and the investigations revealed an enhanced transdermal flux (8.91±0.9 μg/cm2/hr) and decrease lag time (0.9 hr) for Stavudine. The obtained flux was nearly 7.5 and 12.04 times higher than conventional liposomal formulation bearing Stavudine and plain drug solution. These results suggested that transfersomes are potential vehicles for improved transdermal delivery of Stavudine and Span 80, Tween 80 and Sodium cholate were equivalent to Sodium deoxycholate as edge-activators.

Optimization of eugenol microemulsion for transdermal delivery of indomethacin

The aim was to optimize eugenol microemulsion for transdermal delivery of indomethacin (model drug). Pseudo-ternary phase diagrams were constructed using Tween 40 (surfactant) in presence and absence of ethanol or propylene glycol (PG) as co-surfactants. Microemulsion formulations containing eugenol at 10, 20 and 30% w/w with 60% w/w of surfactant or surfactant/co-surfactant were evaluated for indomethacin loading, release and transdermal delivery. Transdermal delivery was assessed using rabbit ear model. The phase diagrams reflected the ability of Tween 40 to form eugenol microemulsion with addition of ethanol or PG increasing the microemulsion zone. Indomethacin loading in microemulsion was increased by increasing eugenol concentration and in presence of co-surfactants. The release rate increased in presence of PG or ethanol. Indomethacin transdermal flux was greater from microemulsions containing high eugenol concentration with PG containing systems being superior. The study introduced eugenol microemulsion formulations for transdermal delivery and highlighted possible synergism with PG.

Nanoemulsion-based film formulation for transdermal delivery of carvedilol

The objective of the present study was to investigate an oil in water nanoemulsion-loaded film as a transdermal delivery vehicle for the poorly-soluble drug, carvedilol. An optimized carvedilol-loaded nanoemulsion containing 10% w/w oil phase, 50% w/w surfactant: cosurfactant and 40% water was selected based on various parameters, including nanoemulsion mean droplet size, clarity, stability, and flowability, and this was then incorporated into the film. Carvedilol-loaded nanoemulsion films were prepared from 55% w/w hydroxypropyl methylcellulose (HPMC), 23% w/w chitosan, 5% w/w isopropanol and 17%w/w carvedilol-loaded nanoemulsion at a concentration of 25 mg/ml. Films were characterized for weight variation, thickness, moisture content and drug-excipient incompatibility. In addition, the in-vitro release of carvedilol from these films was determined using Franz diffusion cells and compared to control film prepared from aqueous blends containing 55% w/w HPMC, 23% w/w chitosan, 5% w/w isopropanol and 17%w/w polyethylene glycol (PEG 400) in which carvedilol was dissolved in PEG 400 at the same concentration of 25 mg/ml. Significant increases in the steady state flux (Jss), permeability coefficient (p) and flux enhancement ratio were observed in the nanoemulsion-based film (p < 0.05), when compared to the control film. These results suggest that nanoemulsion could be used as a potential vehicle for improved transdermal delivery of carvedilol.

Improving the skin penetration and antifebrile activity of ibuprofen by preparing nanoparticles using emulsion solvent evaporation method

Ibuprofen (IBU) is an effective analgesic, non-steroidal anti-inflammatory drug. Unfortunately, oral IBU can cause adverse gastrointestinal drug reactions, such as bleeding and ulcerations, and increases the risk for stomach or intestinal perforations. In this study, IBU nanoparticles (IBU-NPs) were prepared through emulsion solvent evaporation and freeze-drying to improve their solubility. IBU nanoemulsion and nanosuspension were optimized through a single-factor experiment. IBU-NPs with a mean particle size of 216.9±10.7nm were produced under optimum conditions. These IBU-NPs were characterized by using scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, and residual solvent determination to determine their solvent residue, equilibrium solubility, dissolution rate, in vitro transdermal rate, transdermal bioavailability, and antifebrile experiment for febrile rats. The morphological characteristic of IBU-NPs showed porous clusters. Analysis results indicated that the prepared IBU-NPs have low crystallinity. Residual amounts of ethanol and chloroform were 170 and 9.6ppm, respectively, which were less than the ICH limit for class II. Measurement analysis showed that the IBU-NPs were converted underwent amorphous states after preparation, but the chemical structure of the IBU-NPs was unchanged. Transdermal bioavailability of IBU in the IBU-NP group improved significantly compared with oral and transdermal raw IBU. Furthermore, the IBU-NP transdermal gel exhibited a high and stable cooling rate and a long cooling duration in febrile rats. In comparison with the raw oral IBU and raw IBU transdermal gel, the IBU-NP transdermal gel manifested better efficacy at low and mid doses. Basing from the results, we conclude that IBU-NPs can be applied in transdermal delivery formulations and have potential application value for non-oral administration.

Development of a nanogel formulation for transdermal delivery of tenoxicam: a pharmacokinetic–pharmacodynamic modeling approach for quantitative prediction of skin absorption

This study investigates potentials of solid lipid nanoparticles (SLN)-based gel for transdermal delivery of tenoxicam (TNX) and describes a pharmacokinetic–pharmacodynamic (PK–PD) modeling approach for predicting concentration–time profile in skin. A 23 factorial design was adopted to study the effect of formulation factors on SLN properties and determine the optimal formulation. SLN-gel tolerability was investigated using rabbit skin irritation test. Its anti-inflammatory activity was assessed by carrageenan-induced rat paw edema test. A published Hill model for in vitro inhibition of COX-2 enzyme was fitted to edema inhibition data. Concentration in skin was represented as a linear spline function and coefficients were estimated using non-linear regression. Uncertainty in predicted concentrations was assessed using Monte Carlo simulations. The optimized SLN was spherical vesicles (58.1 ± 3.1 nm) with adequate entrapment efficiency (69.6 ± 2.6%). The SLN-gel formulation was well-tolerated. It increased TNX activity and skin level by 40 ± 13.5, and 227 ± 116%, respectively. Average Cmax and AUC0–24 predicted by the model were 2- and 3.6-folds higher than the corresponding values computed using in vitro permeability data. SLN-gel is a safe and efficient carrier for TNX across skin in the treatment of inflammatory disorders. PK–PD modeling is a promising approach for indirect quantitation of skin deposition from PD activity data.

Permeation of sumatriptan succinate across human skin using multiple types of self-dissolving microneedle arrays fabricated from sodium hyaluronate

Available formulations of sumatriptan succinate (SS) have low bioavailability or are associated with site reactions. We developed various types of self-dissolving microneedle arrays (MNs) fabricated from sodium hyaluronate as a new delivery system for SS and evaluated their skin permeation and irritation in terms of clinical application. In vitro permeation studies with human skin, physicochemical properties (needle length, thickness and density), and penetration enhancers (glycerin, sodium dodecyl sulfate and lauric acid diethanolamide) were investigated. SS-loaded high-density MNs of 800 µm in length were the optimal formulation and met clinical therapeutic requirements. Penetration enhancers did not significantly affect permeation of SS from MNs. Optical coherence tomography images demonstrated that SS-loaded high-density MNs (800 µm) uniformly created drug permeation pathways for the delivery of SS into the skin. SS-loaded high-density MNs induced moderate primary skin irritations in rats, but the skin recovered within 72 h of removal of the MNs. These findings suggest that high-density MNs of 800 µm in length are an effective and promising formulation for transdermal delivery of SS. To our knowledge, this is the first report of SS permeation across human skin using self-dissolving MNs.

Optimization of elastic transfersomes formulations for transdermal delivery of pentoxifylline

Pentoxifylline (PTX) is a xanthine derivative indicated in treatment of intermittent claudication and chronic occlusive arterial diseases. It has low oral bioavailability and short half-life; thus, it was considered as a good candidate drug for the transdermal transfersomes formulation. In the present study, an attempt has been made for development, in-vitro and in-vivo evaluation of transdermal transfersomes using sodium cholate (SC) and non-ionic surfactants as edge activators. The optimal formulation, F4(Gcholate), exhibited drug entrapment efficiency of 74.9±1.6%, vesicles elasticity of 145±0.6 (mgs−1cm−2), zeta potential of −34.9±2.2mV, average vesicle diameter of 0.69±0.049μm with PDI of 0.11±0.037 and permeation flux of 56.28±0.19μgcm−2h−1. It attained a prolonged drug release where 79.1±2.1% of PTX released after 10h of the run. The drug release kinetic obeys Higuchi model (R2=0.997) with Fickian diffusion mechanism. Moreover, the formula enhanced drug permeation through the excised rat’s skin predominantly via the carrier-mediated mechanism by 9.1 folds in comparison with the control. Results of the in vivo pharmacokinetics study in male volunteers showed that F4(Gcholate) transfersomes formulation increased PTX absorption and prolonged its half-life comparing to the commercial oral SR tablets. Hence, the elastic transfersomes formulation of PTX possesses admirable potential to avoid drug metabolism, improve PTX bioavailability and sustain its release.

Topical Analgesics: Critical Issues Related to Formulation and Concentration

Topical analgesics are in need to be differentiated from transdermal formulations of analgesics. Topical analgesics are characterized by local analgesic effects in the absence of systemic effects, and do not require a transdermal delivery formulation. There are two key issues in the development of topical analgesics. 1. For optimal clinical effects specific characteristics for the vehicle (a cream base or gel base) are required, depending on the physicochemical characteristics of the pharmaceutical active ingredient in the carrier. 2. One cannot and should not skip well designed phase II dose-finding studies, and this unfortunately happens often, as we will discuss in this paper. In fact, we will demonstrate underdosing is one of the major hurdles to detect meaningful and statistically relevant clinical effects of topical analgesics. In the case of gels or creams containing ketamine, amitriptyline and baclofen, the dose-finding most probably needs to start at 10% for ketamine and amitriptyline and 2.5% for baclofen, while the doses tested were much lower: 4%, 2% and 1% respectively. Topical analgesics are promising inroads for the treatment of neuropathic pain, once sufficient attention is given to aspects such as formulation and concentration.

Nano-transfersomal formulations for transdermal delivery of asenapine maleate: in vitro and in vivo performance evaluations

Context: Asenapine maleate (ASPM) is an antipsychotic drug for the treatment of schizophrenia and bipolar disorder. Extensive metabolism makes the oral route inconvenient for ASPM.Objective: The objective of this study is to increase ASPM bioavailability via transdermal route by improving the skin permeation using combined strategy of chemical and nano-carrier (transfersomal) based approaches.Materials and methods: Transfersomes were prepared by the thin film hydration method using soy-phosphatidylcholine (SPC) and sodium deoxycholate (SDC). Transfersomes were characterized for particle size, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, surface morphology, and in vitro skin permeation studies. Various chemical enhancers were screened for skin permeation enhancement of ASPM. Optimized transfersomes were incorporated into a gel base containing suitable chemical enhancer for efficient transdermal delivery. In vivo pharmacokinetic study was performed in rats to assess bioavailability by transdermal route against oral administration.Results and discussion: Optimized transfersomes with drug:SPC:SDC weight ratio of 5:75:10 were spherical with an average size of 126.0 nm, PDI of 0.232, ZP of −43.7 mV, and entrapment efficiency of 54.96%. Ethanol (20% v/v) showed greater skin permeation enhancement. The cumulative amount of ASPM permeated after 24 h (Q24) by individual effect of ethanol and transfersome, and in combination was found to be 160.0, 132.9, and 309.3 μg, respectively, indicating beneficial synergistic effect of combined approach. In vivo pharmacokinetic study revealed significant (p < 0.05) increase in bioavailability upon transdermal application compared with oral route.Conclusion: Dual strategy of permeation enhancement was successful in increasing the transdermal permeation and bioavailability of ASPM.

Physicochemical, in vitro and in vivo evaluation of flurbiprofen microemulsion.

Flurbiprofen, a potent nonsteroidal anti-inflammatory drug, is widely used for relief of pain in patients suffering from rheumatic diseases, migraine, sore throat and primary dysmenorrheal. However, this drug has many gastrointestinal side effects produced by its oral administration, such as gastric bleeding and peptic ulcer. These effects were responsible for non-compliance among patients, which ultimately results in treatment failure. The physicochemical properties of flurbiprofen, make it a suitable candidate for transdermal drug delivery, which can overcome the drawbacks of oral administration. In this sense, microemulsions have been proved to increase the cutaneous absorption of lipophilic drugs when compared to conventional drug delivery systems. The purpose of this study was to formulate and characterize gel based microemulsions, for topical delivery of flurbiprofen. Different gel bases, containing microemulsion and hydro-alcoholic solution of flurbiprofen, were developed and compared. In vitro study showed that gels containing microemulsion had a higher permeation rate than those containing hydro-alcoholic solutions. Additionally, formulation of Carbopol-I (microemulsion) showed higher percent of inhibition of inflammation than others bases. Further, skin irritation study demonstrated that Carbopol-I was none irritating. Flurbiprofen microemulsion incorporated on Carbopol-I showed physicochemical, in vitro and in vivo characteristics suitable for the development of alternative transdermal delivery formulation.