Permeation Percentage Research Articles

Enhancing the Solubility and Transdermal Delivery of Drugs Using Ionic Liquid‐In‐Oil Microemulsions

AbstractThe development of hydrophobic drug and protein delivery carriers remains a challenge. To synthesize L‐(‐)‐carnitine‐based ionic liquid (IL), this study applies the density functional theory to investigate the hydrogen bonds and van der Waals force that govern L‐(‐)‐carnitine‐based IL formation. An ionic liquid‐in‐oil microemulsion (IL/O ME) is then developed to facilitate the transdermal delivery of proteins and increase the solubility of drugs. IL/O ME is prepared using isopropyl myristate (IPM), Tween 80/Span 20, and L‐(‐)‐carnitine‐based IL. The skin permeation studies conducted using mouse skin show that the insulin permeation percentage of the developed IL/O ME is 3.55 folds higher than that of phosphate‐buffered saline and 2.91 folds better than that of a hydrophilic L‐(‐)‐carnitine‐based IL. In addition, the solubility of two drug molecules, that is, rosiglitazone and bezafibrate, in IL/O ME is at least 49.28 folds higher than their solubility in water or IPM. Therefore, IL/O ME can significantly improve the solubility of drugs and increase the permeability of proteins (e.g., insulin), thus demonstrating a promising potential as a delivery carrier.

Development and Characterization of Orally Dissolving Tablet of a Poorly Soluble Antiemetic Drug

The aim of present work is to prepare the orally dissolving tablets of poorly soluble Ondransetron Hydrochloride as its soluble form by adopting complexation method using different superdisintegrants alone and in combination. The growing importance of orally dissolving tablet was underlined recently when European Pharmacopoeia adopted the term “Oro dispersible tablet” as a tablet that to be placed in the mouth where it disperses rapidly before swallowing. Their characteristic advantages such as administration without water anywhere, anytime lead to their suitability to geriatric and paediatric patients. The complex prepared was showed better solubility in simulated salivary PH of 6.8. The pre compression characteristics of drug, drug with Beta cyclodextrin and final blend were evaluated with respect to standards. Results of the study showed that the optimized tablet with combination of superdisintegrants (2.5% crosspovidone, 3.5% sodium starch glycolate) showed hardness of 3.5Kg/Cm2, thickness 2.10mm, wetting time 18 sec, drug content 99.15%, disintegration time 20sec, in-vitro dispersion time 25sec, in-vitro drug release of 89.59% (in 3min) and percentage of drug permeation as 89.45% (in 5 min) and it is comparable with higher percentage of superdisintegrants used for tablet preparation. So this method was a promising approach for developing cost effective dosage form with high efficacy in treatment.

Fluorescent Sizing Agents Based on Aggregation-Induced Emission Effect for Accurate Evaluation of Permeability and Coating Property

Warp sizing is the most important process of weaving preparation in the textile industry. Permeating and coating of sizing paste into/on warp yarns directly determine the quality of sized yarns. However, there are many significant drawbacks, such as low accuracy and narrow variety adaptability for sizing agents and warp yarns, in the traditional determination method of permeation and coating property of sizing paste. Focusing on the problem, this investigation introduced aggregation-induced emission (AIE) fluorogen to prepare a fluorescent sizing agent. The interface of sizing agent in textile could be accurately visualized by AIE fluorogen. The three indexes to indicate the permeability and coating property of sizing paste, i.e. permeation percentage, coating percentage and integrity percentage of sizing film, have been determined accurately and conveniently. This investigation efficiently solves the difficult problem of evaluating permeation and coating property of sizing paste and has a significant guiding function on accurate determination of the quality of sized yarns.

Self-Nanoemulsion Loaded with a Combination of Isotretinoin, an Anti-Acne Drug, and Quercetin: Preparation, Optimization, and In Vivo Assessment.

Acne vulgaris is a common skin disease that affects everybody at least once in their lives. The treatment is challenging because the stratum corneum contains rigid corneocytes surrounded by intercellular lamellae that are difficult to bypass. In the present study, we intended to formulate an effective nanoemulsion that could deliver isotretinoin (ITT) with enhanced solubility, permeability, and bioavailability across the skin. ITT can have a serious hepatotoxic effect if given too frequently or erratically. Therefore, to overcome the aforesaid limitation, quercetin (QRS), a hepatoprotective agent, was incorporated into the formulation. Initially, the ITT solubility was determined in various surfactants and cosurfactants to select the essential ingredients to be used in the formulation and to optimize a nanoemulsion that could enhance the solubility and permeability of ITT and its antimicrobial activity against Staphyloccocus aureus, which is the main microorganism responsible for acne vulgaris. The mixture design was applied to study the interactions and optimize the independent variables that could match the prerequisites of selected dependent responses. A formulation containing 0.25 g of rosehip oil, 0.45 g of surfactant (Lauroglycol-90), and 0.3 g of cosurfactant (propylene glycol) was chosen as an optimized desirable formulation. The optimized batch was loaded with QRS and evaluated for in vitro and ex vivo permeation. The in vivo hepatotoxicity was assessed through topical administration. Permeability studies confirmed the enhanced permeation percentage of ITT (52.11 ± 2.85%) and QRS (25.44 ± 3.18%) of the optimized formulation, with an enhanced steady-state flux (Jss). The in vivo studies conducted on experimental animals demonstrated superior hepatoprotective activity of the prepared optimized formulation compared with other formulations of drugs and commercially marketed products. We anticipate that this optimized ITT formulation, followed up with good clinical evaluations, can be a breakthrough in the safe treatment of acne vulgaris.

The relevance of nanotechnology, hepato-protective agents in reducing the toxicity and augmenting the bioavailability of isotretinoin

Acne Vulgaris is one of the most common chronic inflammatory skin disorders that affect majority of teen-agers worldwide. Isotretinoin (ITT) is the drug of choice in the management of acne, but, it suffers from serious side-effects including hepatotoxicity, and some psychological disturbances following its oral intake. The objective of this study was to develop and optimize ITT loaded nanoemulsions (ITT-SNEDDS) and to incorporate resveratrol (RSV)in optimum formulation to decrease ITT side effects The ITT solubility was first tested in various essential oils, surfactants, and co-surfactants to select the essential nanoemulsion ingredients. Mixture design was applied to study the effect of independent variables and their interactions on the selected dependent responses. The developed ITT-SNEDDS were characterized for their globule size and ex vivo permeation. The optimized batch was further loaded with RSV and evaluated for in vitro and ex vivo permeation and for in vivo hepatotoxicity. The developed ITT-SNEDDS exhibited globule size below 300 nm, up to 272.27 ± 7.12 mcg/cm2.h and 61.27 ± 2.83% of steady-state flux (JSS) and permeability % respectively. Optimum formulation consisted of 0.15 g oil mixture, 0.6 g of surfactant (Labrasol), and 0.250 g co-surfactant (Transcutol). Permeability studies confirmed the enhanced permeation percentage of ITT (40.77 ± 1.18%), and RSV (29.94 ± 2.02%) from optimized formulation, with enhanced steady-state flux (JSS). In vivo studies demonstrated the superior hepatoprotective activity of optimized formulation compared to a different drug formulations and marketed product. Therefore, RVS loaded ITT-SNEDDS might be a successful strategy for acne management with improved action, and minimum side effects.

Graphene oxide reinforced nanocomposite oleogels improves corneal permeation of drugs

The research on ocular drug delivery (ODD) has attracted a continual interest of researchers in the last decade. Herein, we propose to develop oleogel-based formulations for ODD applications. A series of novel nanocomposite oleogels of groundnut oil (GNO) and stearic acid (SA) were prepared, which contained graphene oxide (GO) in the concentration range of 0.00 wt% and 0.05 wt%. The pristine oleogel appeared yellowish-white. However, an increment in the GO content correspondingly imparted a black color hue to the oleogels. Confocal microscopy suggested a considerable branching of the fibrillar network of the fat crystals at lower concentrations of GO. FTIR spectroscopy revealed that GO did not tailor the interactions among the functional groups that are present within the different components of the oleogels. The X-ray diffraction study suggested that the oleogel with the highest GO content was the most crystalline in nature and had a low lattice strain. The mechanical stability of the oleogels was significantly increased when the GO concentration was >0.015 wt%. Thermal analysis of the oleogels confirmed the crystallization of SA in different polymorphic forms. Furthermore, the thermal stability of the fat network structure was higher in the nanocomposite oleogels. The rate of crystallization of SA was higher in the GO-containing oleogels. In general, the in vitro release and ex vivo corneal permeation of the model antibacterial drug (Ciprofloxacin HCl) from the prepared oleogels was Fickian diffusion mediated. Oleogel that contained 0.015% of GO exhibited a ~2.00 fold increase in the cumulative percentage of drug release. The cumulative percentage of drug permeation through caprine cornea was increased by ~2.00 folds in the oleogel that contained 0.05% of GO. The prepared oleogels were cytocompatible with human mesenchymal stem cells. The drug-loaded oleogels showed good bactericidal activity against E. coli. In conclusion, GNO/SA/GO-based nanocomposite oleogels were found to have the potential to be explored for ODD applications.

Optimizing ophthalmic delivery of a poorly water soluble drug from an aqueous in situ gelling system

Poorly soluble drugs are often unsuitable to incorporate in ocular in situ gelling systems due to the aqueous based gelling formulations and low volumes administered. For such formulations to be successful, the administered drug must have sufficient solubility to diffuse from the formulation to the eye and should not affect the gelation of the in situ gelling material. Drug salt forms can improve the solubility of poorly soluble drugs, however, as in situ gel forming formulations are often designed to be crosslinked by salts (present the lacrimal fluid) it can make salt forms difficult to formulate. The aim of this study was to develop an in situ gel forming ophthalmic formulation of a poorly soluble drug flurbiprofen (FBP) through cyclodextrin complex formation and to analyse the impact on gelation, release and permeation through the cornea. Hydroxypropyl-beta-cyclodextrin (HβCD) was used as a complexing agent and low acyl gellan gum was added to the FBP- HβCD complex as a water soluble in situ gelling polymer. Measurements were performed using rheo-dissolution, which utilises a rheometer with a modified lower plate that has the unique ability to allow rheological measurement and analysis of drug release simultaneously. An ex-vivo permeation study was also performed using porcine cornea. Rheological measurements in terms of elastic (Gʹ) and viscous (G″) modulus showed rapid gelation of the formulation upon contact with simulated lacrimal fluid (SLF). Approximately, 97% FBP was released when 10% HβCD was used and release was decreased to 79% when the amount of HβCD was increased to 20%. The percentage of drug permeation through the cornea was 55% in 300 min whereas the marketed non gelling eye drop formulation containing FBP sodium showed only 37% permeation. The data presented here, revealed that not only could a poorly soluble drug be complexed with cyclodextrin and loaded into an in situ gelling system without interfering with the gelation, but also permeability the of the drug improved.

Perylene-Based Fluorescent Sizing Agent for Precise Evaluation of Permeability and Coating Property of Sizing Paste

Warp sizing is considered as the most important process of weaving preparation in the textile field. The quality of sized warp yarns is directly determined by the permeation and coating of sizing paste into/on warp yarns. However, many significant flaws of the current method of permeability and coating property of sizing paste, such as low accuracy and narrow variety adaptability for sizing agents and warp yarns, have emerged in the evaluation process. In order to eliminate the inherent flaws in the current method, the investigation chose chitosan (CS) as a representative of common sizing agents, introduced various amounts of perylene units onto molecular chains of the CS, and prepared a new functional sizing agent—fluorescent CS with different labeling degrees of perylene. Furthermore, PVA-perylene was synthesized to evaluate the permeability and coating property of PVA sizing paste. Then, three indexes to indicate the permeability and coating property of sizing paste, i.e. permeation percentage, coating percentage and integrity percentage of sizing film, were evaluated using the CS-perylene and PVA-perylene derivatives prepared. Due to the fluorescence emitted by the perylene units, the three indexes can be determined accurately and conveniently depending on only fluorescent microscope and common image processing software. The investigation efficiently solves the difficult problem of evaluating permeation and coating property of the pastes of both bio-based and petroleum-based sizing agents with appropriate degrees of labeling and has a significant guiding function on accurate determination of the quality of sized yarns.

Synthesis of Polyurethane Hydrogel and Polyurethane Thermoplastic Elastomer Composite Based Separation Membranes.

A series of polyurethane hydrogel and polyurethane thermoplastic elastomer composite based separation membranes were successfully prepared via wet phase inversion method. The morphology, chemical structure, phase transition temperature and crystallinity of the polyurethane (PU) membranes were characterized by SEM, FTIR, DSC, and XRD, respectively. The SEM observation showed that the PU membranes exhibited irregular porous structure on the surface and path of the hole was flexural and asymmetrical in cross-section. The FTIR analysis demonstrated that thermalsensitive groups and pH-sensitive components (-N(CH₃)-) were incorporated into the PU network. The DSC experiment and XRD experiment showed that the regular arrangement of PU network was destroyed partly due to the introduction of polyurethane thermoplastic elastomer. The equilibrium swelling ratio (ESR) and water flux (J) for PU membranes clearly decreased and increased with functional groups and sophisticated structure of PU membranes, respectively. In addition, the permeation experiments indicated that the permeation percentage (P) of the glycine was strongly affected by the external temperature and pH value.

Topical monomethylsilanetriol can deliver silicon to the viable skin.

Organic silicon has been linked to positive effects on the skin rejuvenation, mainly by the oral route. Thus, the main objective of the present study was to assess whether monomethylsilanetriol (MMST, a source of organic silicon) can deliver silicon to the epidermis and dermis, when applied topically in a cream. Once the hypothesis was confirmed, the present study also evaluated whether the product was toxic to keratinocytes; additionally, its possible antioxidant activity was assessed. The ex vivo skin permeation profile was determined using human skin in Franz-cells equipment; cytotoxicity was assessed using HaCaT keratinocytes. Antioxidant capacity was determined as scavenging activity, measured according to the 1,1-diphenyl-2-picrylhydrazil free radical method. The permeation percentage was almost 60% of the applied MMST, with a large quantity of drug found in the viable epidermis and dermis. The cell viability assay showed no significant difference in the percentage of viable keratinocytes among the treated groups at the doses used. In terms of antioxidant activity, the IC50 value obtained was 2400μgmL-1 . Low antioxidant activity, negligible toxicity for keratinocytes and a significant percentage of permeation were observed. We provide evidence that MMST applied topically can deliver silicon to the skin in biorelevant levels for cosmetic purposes.

Formulation and Evaluation of Ketoprofen Gel Preparations, Sesami Oil Soybean Oil and Oleic Acid as Enhancers

Permeation is a measurable profile in drug penetration in skin. Adding increasing permeation substance (enhancer) in drug formulation is an important thing in pharmaceutical and toxicology in nowadays. The purpose of this research was to evaluate the effect of sesame oil, soybean oil, and oleic acid as enhancer in ketoprofen gel permeation. Six formula were prepared by varying concentration of sesame oil, soybean oil, and oleic acid respectively 5% and 10% and one blank, without enhancer. Permeation test was evaluated by in vitro permeation test using Franz diffusion cell method and shed snake skin of reticulated python as a membrane. Permeation test were carried out for 6 hours. The result showed that sesame oil, soybean oil, and oleic acid were able to increase ketoprofen permeation. B1 formula that contain 5% sesame oil had greatest percent permeation after 6 hours is 5.913%, while blank that contain no enhancer is 0.623%.Keywords: ketoprofen, permeation, enhancer, soybean oil, sesame oil, oleic acid.

FORMULATION AND EVALUATION OF GEL CONTAINING ETHOSOMES ENTRAPPED WITH TRETINOIN

A skin disease, like acne, is very common and normally happens to everyone at least once in their lifetime. The structure of the stratum corneum is often compared with a brick wall, with corneocytes surrounded by the mortar of the intercellular lipid lamellae. One of the best options for successful drug delivery to the affected area of skin is the use of ethosomes which can be transported through the skin through channel-like structures. Tretinoin is a widely used retinoid for the topical treatment of acne, photo-aged skin, psoriasis and skin cancer which makes it a good candidate for topical formulation. Yet side effects, like redness, swelling, peeling, blistering and, erythema, in addition to its high lipophilicity make this challenging. Drug loaded ethosomes had been prepared using phospholipid and ethanol, were optimized and characterized for entrapment efficiency, vesicular size, shape, In-vitro skin permeation, skin retention, drug‐membrane component interaction and stability. The ethosomal formulation having 0.5 %w/v of phospholipid and 20 %v/v of ethanol (F2) showing the greatest entrapment efficiency (80.25±0.23) with small particle size (205.40±2.31nm) was selected for further skin permeation studies. The skin permeation and skin retention studies were performed on ethosomal formulation, liposomal formulation (0.5 %w/v of phospholipid without alcohol), hydroethanolic drug solution and phosphate buffer saline (pH7.4) drug solution. Among them, ethosomal formulation showed higher cumulative percentage of drug permeation (93.36±0.45%) and 8 hours than the other formulations. Scanning electron microscopy confirmed the three dimensional nature of ethosomes. Dynamic light scattering technique proved that the ethosomes has smaller vesicular size than the liposomes prepared without alcohol. FT‐IR studies revealed no interaction between the drug and membrane components. The ethosomal vesicles were incorporated in carbopol gel base and its anti‐acne was compared with the marketed gel. Our results suggest that the ethosomes are an efficient carrier for dermal and transdermal delivery of tretinoin.
 Keywords: Tretinoin, Ethosomes, Diffusion, Carbopol gels, Transdermal delivery.

The Effect of Prim-O-Glucosylcimifugin on Tryptase-Induced Intestinal Barrier Dysfunction in Caco-2 Cells.

The intestinal barrier dysfunction is a critical pathological change in irritable bowel syndrome (IBS). The objective of this study was to evaluate the effect of Prim-O-glucosylcimifugin (POG) on intestinal barrier dysfunction and reveal possible molecular mechanisms. Human colon adenocarcinoma cell line (Caco-2) cell monolayers induced by tryptase (TRYP) were used to establish an intestinal barrier dysfunction model. Caco-2 cell monolayers from both functional and dysfunctional samples were treated with POG (30, 60 and 120 µg/mL) for 2, 8, 24, 36, 48 and 72 h. The Caco-2 cell monolayers were assessed by measurement of trans-epithelial electrical resistance (TEER) and percentage of fluorescein permeation (PFP). The expression of Protease Activated Receptor 2 (PAR-2) and myosin light chain kinase (MLCK) mRNA was analyzed by RT-PCR and the level of Zonula Occludens-1 (ZO-1) protein expression was determined by Western blot. In addition, the impact of POG on the distribution of the tight juction protein of Occludin was performed by immunofluorescence. Our results showed that POG elevated the TEER and decreased the PFP of the functional Caco-2 cell monolayers, as well as the dysfunctional Caco-2 cell monolayers. Furthermore, POG inhibited the expression of PAR-2 mRNA and MLCK mRNA and increased the level of ZO-1 protein expression in dysfunctional Caco-2 cells. The distribution of the Occludin proteins was ameliorated simultaneously. This study demonstrates that POG can enhance the intestinal barrier function of Caco-2 cell monolayers by inhibiting the expression of PAR-2 and MLCK and up-regulating the expression of ZO-1 protein, and ameliorated the distribution of Occludin protein.

In vitro Permeation Study of Ketoprofen Patch with Combination of Ethylcellulose and Polyvynil Pyrrolidone as Matrix Polymers

Objective: Transdermal patch can release drug to provide systemic pharmacological effect. Matrix used in the patch formula influences the release of the drug. The aim of the study was to evaluate permeation of Ketoprofen patch containing combination of Ethyl Cellulose (EC) and Polyvynil Pyrrolidone (PVP) as matrix. EC is a hydrophobic polymer while PVP is a hydrophilic one. Transdermal formulation containing two polymers with different polarity will provide better permeation results than use only one type of polymer. Ketoprofen 1% was used as a model of active substance in the study. Methods: Ratio of EC and PVP concentration (1:1, 1:3 and 3:1) in patch formula was determined using Simplex Lattice Design (SLD) method. In vitro permeation study was done for 12 h using Franz diffusion cell and shed snake of Phyton reticulatus as a membrane. Amount of the drug released was analyzed using Spectrophotometer UV-Vis (λ = 262 nm). The drug release mechanism was known by determination the drug release kinetics order. Results: The study result showed that the higher PVP concentration was used in the formula, the higher percentage of Ketoprofen permeation was obtained. Patch formula containing EC:PVP in ratio 1:3 had the highest percentage of permeation (93.66%). The drug release kinetics of Ketoprofen from the patch followed zero order kinetics. Conclusion: Combination of EC and PVP in ratio 1:3 resulted the highest percentage of ketoprofen permeation for 12 h (93.66%). The drug release mechanism followed zero order kinetics. Key words: Ethylcellulose, Ketoprofen, Patch, Permeation, Polyvynil pyrrolidone, Simplex Lattice Design.

Mucus permeating self-emulsifying drug delivery systems (SEDDS): About the impact of mucolytic enzymes

This study aimed to improve the mucus permeating properties of self-emulsifying drug delivery systems (SEDDS) by anchoring lipidized bromelain, papain and trypsin using palmitoyl chloride. SEDDS containing enzyme-palmitate conjugates were characterized regarding droplet size and zeta potential. Their mucus permeating properties were evaluated by Transwell diffusion and rotating tube method using fluorescein diacetate (FDA) as marker. Degree of substitution of modified enzymes was 35.3%, 47.8% and 38.5% for bromelain-palmitate, papain-palmitate and trypsin-palmitate, respectively. SEDDS as control and SEDDS containing enzyme-palmitate conjugates displayed a droplet size less than 50nm and 180–312nm as well as a zeta potential of −3 to −4 and −4 to −5mV, respectively. The highest percentage of permeation was achieved by introducing 5% papain-palmitate into SEDDS. It could enhance the mucus permeation of SEDDS in porcine intestinal mucus 4.6-fold and 2-fold as evaluated by Transwell diffusion and rotating tube method, respectively. It is concluded that mucus permeation of SEDDS can be strongly improved by incorporation of enzyme-palmitate conjugates.

Surface-tailored nanomixed micelles containing quercetin-salicylic acid physical complex for enhanced cellular and in vivo activities: a quality by design perspective.

The development of surface-tailored quercetin (QCT)-salicylic acid (SA) physical complex for effective treatment of skin carcinoma. QCT-SA nanomixed micelles were prepared by the self-assembly method employing the Quality by Design (QbD) approach and evaluated for various in vitro, ex vivo and in vivo parameters. The optimized formulation showed enhanced percent permeation (Q24), in other words, 78.12 ± 0.47, improved in vitro cellular uptake and annexin-V-apoptosis assay exhibited 60.86% cell death. The 7,12-dimethylbenz(a)anthracene and histopathology protocol revealed the improved antineoplastic action of QCT. The dermatokinetic profile showed the maximum drug concentration (6 h), in other words, 416.02 ± 26 μg/cm2 in epidermis and 103.65 ± 12 μg/cm2 in dermis. The overall performance ratified the safety and efficacy of optimized nanomixed micelless of QCT with SA in a synergistic manner.

Two steps modification for improvement of cyclobenzaprine transdermal delivery: releasing from patch and penetrating through skin

The aim of this study was to improve the transdermal delivery of cyclobenzaprine (CBZ) from drug-in-adhesive patch which showed less side effects and better compliance. CBZ base was prepared and then characterized using differential scanning calorimetry (DSC). The interaction between CBZ and pressure-sensitive adhesive (PSA) was determined by Fourier Transform Infrared Spectroscopy (FT-IR). The influences of PSAs, penetration enhancers, patch thickness and drug content on the transdermal delivery of CBZ were studied thoroughly in vitro. Both CBZ releasing from patch and penetrating through the skin showed very great effect on the transdermal delivery of CBZ. The percentage of drug released from patch was increased with the decreasing of patch thickness, and so did the permeation percentage. The stratum corneum (SC) contributed approximately 57% resistance of total skin permeation resistance, and Span 20 increased the transdermal permeation by approximately 1.59-fold. The pharmacokinetic parameters were obtained through in vivo experiments of the optimized formulation using rabbit. Furthermore, the in vitro skin permeation results of CBZ patch correlated well with the in vivo absorption results in rabbit.

Effect of Formulation Factors on Transcorneal Permeation of Acetazolamide from Aqueous Drops: In vitro andIn vivo Study

Aim: The purpose of this research was to evaluate the effect the formulation factors on in vitro permeation of acetazolamide (ACZ) through freshly isolated goat corneas. Materials and Methods: Different formulation factors were studied. The concentration of drug was raised from 0.025% to 0.1% (w/v) and pH was also varied within the range of 6-8. Several viscosity modifiers and preservatives were also added to study their effect on permeation. Finally, the formulation with the optimized factors was used to study ocular hypotensive activity of the drug in rabbits. Results and Discussion: Raising concentration of the drops from 0.025% to 0.1% (w/v) significantly (P < 0.05), increased drug permeation, but decreased the percent permeation. An increase in the pH of the drops from 6.0 to 8.0 resulted in significant (P < 0.05) change in drug permeation. Eye drops containing benzalkonium chloride (BKC) showed significantly (P < 0.05) higher permeation as compared with control formulation. Compared with control formulation, ACZ 0.1% (w/v) drop containing viscosity modifier produced significant (P < 0.05) decrease in permeation. A formulation having BKC showed increased hypotensive activity as compared to the control formulation. Conclusion: The study reflects that the permeation of ACZ is greatly influenced by formulation factors and permeation was found to be concentration and pH dependent.

An ionic liquid-in-water microemulsion as a potential carrier for topical delivery of poorly water soluble drug: Development, ex-vivo and in-vivo evaluation

In this paper, we report an ionic liquid-in-water (IL/w) microemulsion (ME) formulation which is able to solubilize etodolac (ETO), a poorly water soluble drug for topical delivery using BMIMPF6 (1-butyl-3-methylimidazolium hexafluorophosphate) as IL, Tween 80 as surfactant and ethanol as co-surfactant. The prepared ME was characterized for physicochemical parameters, subjected to ex-vivo permeation studies as well as in-vivo pharmacodynamic evaluation. The ex-vivo drug permeation studies through rat skin was performed using Franz-diffusion cell and the IL/w based ME showed maximum mean cumulative percent permeation of 99.030±0.921% in comparison to oil-in-water (o/w) ME (61.548±1.875%) and oily solution (48.830±2.488%) of ETO. In-vivo anti-arthritic and anti-inflammatory activities of the prepared formulations were evaluated using different rodent models and the results revealed that ETO loaded IL/w based ME was found to be more effective in controlling inflammation than oily solution, o/w ME and marketed formulation of ETO. Histopathological studies also demonstrated that IL/w based ME caused no anatomical and pathological changes in the skin.

Microemulsion-Based Topical Hydrogels of Tenoxicam for Treatment of Arthritis.

Tenoxicam (TNX) is a non-steroidal anti-inflammatory drug (NSAID) used for the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, backache and pain. However, prolonged oral use of this drug is associated with gastrointestinal adverse events like peptic ulceration, thus necessitating its development as topical formulation that could obviate the adverse effects and improve patient compliance. The present study was aimed at development of microemulsion-based formulations of TNX for topical delivery at the affected site. The pseudoternary phase diagrams were developed and microemulsion formulations were prepared using Captex 300/oleic acid as oil, Tween 80 as surfactant and n-butanol/ethanol as co-surfactant. Optimized microemulsions were characterized for drug content, droplet size, viscosity, pH and zeta potential. The ex vivo permeation studies through Laca mice skin were performed using Franz diffusion cell assembly, and the permeation profile of the microemulsion formulation was compared with aqueous suspension of drug and drug incorporated in conventional cream. Microemulsion formulations of TNX showed significantly higher (p < 0.001) mean cumulative percent permeation values in comparison to conventional cream and suspension of drug. In vivo anti-arthritic and anti-inflammatory activity of the developed TNX formulations was evaluated using various inflammatory models such as air pouch model, xylene-induced ear edema, cotton pellet granuloma and carrageenan-induced inflammation. Microemulsion formulations were found to be superior in controlling inflammation as compared to conventional topical dosage forms and showed efficacy equivalent to oral formulation. Results suggest that the developed microemulsion formulations may be used for effective topical delivery of TNX to treat various inflammatory conditions.