Ex-vivo Skin Permeation Studies Research Articles

Optimizing Dermal Delivery of Linezolid for Treating Skin and Soft Tissue Infections: NLC-Based Gel Formulation Using Taguchi Design

Background: Uncomplicated skin and soft tissue infections account for approximately 200 million visits to ambulatory care settings annually. Linezolid (LNZ) is an oxazolidinone that has proven its effectiveness in combating skin and soft tissue infections caused by gram-positive pathogens. LNZ is administered via oral suspension, tablets, or an intravenous route in most in-stances. However, its extended therapy leads to undesirable side effects like diarrhoea, thrombo-cytopenia, myelosuppression, lactic acidosis, etc. and even life-threatening complications. The dermal administration of LNZ offers an alternative route, ensuring localized and sustained release at the site of infection. This approach may reduce systemic exposure and allow for lower doses compared to oral ingestion, which can decrease the risk of adverse effects. Objective: This research aimed to develop a nanostructured lipid carrier (NLC)-based gel for de-livering LNZ via the dermal route to treat uncomplicated skin and soft tissue infections. Methods: NLC were developed by high-shear homogenisation and sonication method using glyc-eryl trimyristate as a solid lipid and neem oil as a liquid lipid. The Taguchi design was employed to optimize NLCs using surfactant concentration (mg), drug-to-lipid ratio, and sonication time (sec) as independent variables. Their effect on particle size, zeta potential, and entrapment effi-ciency was studied. The optimized nanocarriers were developed into a gel product and evaluated for drug release, permeation, and antibacterial activity. Results: The optimised process parameters to attain outcomes were 2% surfactant, 1:1 drug-to-lipid ratio and 300 seconds of sonication. The resulting NLC had an average size of 191.2 ± 2.76 nm, a zeta potential of -30.7 ± 4.50 mV, and 84.89 ± 2.76% drug entrapment. NLC-based gel dis-played anomalous transport with a 90.16 % drug release. The gel showed a strong antibacterial effect against Staphylococcus aureus with a 7.57 ± 0.12 cm mean zone of inhibition. Ex-vivo skin permeation studies revealed 24.19 ± 0.19 % drug permeation and 64.46 ± 0.58% cutaneous depo-sition. NLC-based gel demonstrated a significant decrease in colony-forming units in infected an-imal models. Conclusion: The ex-vivo investigations demonstrated the presence of LNZ at the infection site, enhancing therapeutic effectiveness. In vitro and in-vivo findings illustrated the substantial anti-bacterial efficacy of LNZ NLC-based gel. The adoption of NLC-based gel exhibits promising po-tential as a carrier for dermal delivery of LNZ.

Tailoring of spanlastics for promoting transdermal delivery of irbesartan: In vitro characterization, ex vivo permeation and in vivo assessment

Irbesartan (IRB), a selective AT1 subtype angiotensin II receptor blocker used for management of hypertension, exhibiting low and variable oral bioavailability because of its poor aqueous solubility. Transdermal delivery is increasingly being used to deliver drugs since it avoids the drawbacks associated with oral delivery. The purpose of the current study was to develop a transdermal gel of IRB through encapsulation of the drug into spanlastics vesicles containing penetration enhancers to enhance transdermal permeation and sustain IRB release. By ethanol injection method, ten IRB loaded spanlastics (IRB-SPs) were prepared; Span 60 was used as the main vesicle component and the used edge activator (EA) was Tween 80. The prepared formulations were studied in regards to entrapment efficiency (EE%), particles size (PS), zeta potential (ZP), polydispersity index (PDI), and in vitro release study. The selected formula (SF) which comprised of Span 60 and Tween 80 at weight ratio of 1:1 and Labrafil as a penetration enhancer, exhibited EE% of 90.06 ± 1.44 %, PS of 311.6 ± 2.45 nm, PDI of 0.536 ± 0.044, and the % drug released after 8 h is 58.2 ± 1.87 %. Transmission electron microscopy confirmed the spherical shape of the prepared spanlastics. Differential scanning calorimetry (DSC) confirmed the drug encapsulation within the spanlastics. The SF and pure drug were incorporated into HPMC K4M based hydrogel (2.5 % w/v). Histopathological and ex-vivo skin permeation studies of hydrogel were assessed as well as its in vitro characteristics. Skin permeation was enhanced by 3.5 folds with the SF loaded gel compared to the control gel. The pharmacokinetic study revealed better bioavailability of the SF-gel by 1.72 and 2.53 fold as compared to the oral suspension and the control gel, respectively. Furthermore, the pharmacodynamic assessment was carried out on systolic blood pressure (SBP) of various IRB formulations in dexamethasone induced hypertensive rat; the antihypertensive effect of SF loaded transdermal gel showed significantly (p < 0.001) much greater blood pressure reduction than the market product's oral suspension. Finally, spanlastics-based gels could be an excellent way to improve IRB transdermal delivery.

Berberine HCl and diacerein loaded dual delivery transferosomes: Formulation and optimization using Box-Behnken design.

Berberine is a poorly water-soluble alkaloid compound showing significant anti-inflammatory characteristics. It reduces the levels of pro-inflammatory and inflammatory cytokines, including tumour necrosis factor (TNF-α, IFN-γ) and interleukin (IL-23, IL-12, and IL-23). Diacerein significantly reduces the splenomegaly associated with psoriasis. It downregulates the production of TNF-α and IL-12. This study reported the development of transferosomes containing berberine HCl and diacerein using a film hydration method followed by optimization using a Box-Behnken design. Sodium deoxycholate was used as an edge activator. The impact of independent variables (amount of phosphatidylcholine, amount of edge activator, and sonication cycles) on dependent variables (particle size and entrapment efficiency) was examined. The optimized formulation was characterized for polydispersity index, vesicle size, entrapment efficiency, ζ potential, spectral analysis like Fourier transform infrared, thermal analysis, X-ray diffraction, deformability, transmission electron microscopy, antioxidant assay, in-vitro release, and ex-vivo skin permeation studies. The optimized formulation had a particle size of 110.90±2.8 nm with high entrapment efficiency (89.50±1.5 of berberine HCl and 91.23±1.8 of diacerein). Deformability, polydispersity index, ζ potential, and antioxidant activity of the optimized formulation were 2.44, 0.296, -13.3, and 38.36 %, respectively. Optimized transferosomes exhibited 82.093±0.81 % and 85.02±3.81 % release of berberine HCl and diacerein after 24 h of dissolution study. The transdermal flux of optimized formulation was 0.0224 μg cm-2 h-1 (2.24 cm h-1 permeation coefficient) and 0.0462 μg cm-2 h-1 (4.62 cm h-1 permeation coefficient), respectively, for berberine HCl and diacerein. Raman analysis of treated pig skin confirmed that the transferosomes can permeate the skin. No change in the skin condition or irritation was observed in BALB/c mice. Formulation stored at 4 and 25±2 °C / 60±5 % relative humidity was stable for 3 months. Thus, the results demonstrated successful optimization of the transferosomes for the efficient topical delivery of berberine HCl and diacerein in the effective management of psoriasis.

Optimized Ribociclib nanostructured lipid carrier for the amelioration of skin cancer: Inferences from ex-vivo skin permeation and dermatokinetic studies

Current research focuses on explicitly developing and evaluating nanostructured lipidic carriers (NLCs) for the chemotherapeutic drug Ribociclib (RCB) via the topical route to surmount the inherent bioavailability shortcomings. The absolute oral bioavailability has not been determined, but using a physiologically based pharmacokinetic model it was predicted that 65.8 % of the standard dose of RCB (600 mg) would be absorbed mainly in the small intestine. RCB-NLCs were produced using the solvent evaporation method, and Box-Behnken Design (BBD) was employed to optimize composition. The prepared NLCs had an average PS of 79.29 ± 3.53 nm, PDI of 0.242 ± 0.021, and a %EE of 86.07 ± 3.14. The TEM analysis disclosed the spherical form and non-aggregative nature of the NLCs. The outcomes of an in-vitro release investigation presented cumulative drug release of 84.97 ± 3.37 % in 24 h, significantly higher than that from the RCB suspension (RCB-SUS). Ex-vivo skin permeation investigations on rodent (Swiss albino mice) revealed that RCB-NLCs have 1.91 times increases in skin permeability comparable to RCB-SUS. Compared to RCB-SUS, RCB-NLCs were able to penetrate deeper into the epidermis membrane than RCB-SUS as per the findings of confocal microscopy. In dermatokinetic study, higher amount of RCB was maintained in both the layers of mice's skin when treated with RCB-NLCs gel comparable to the RCB-SUS gel preparation. The in-vitro, ex-vivo, CLSM, and dermatokinetics data demonstrated a significant possibility for this novel RCB formulation to be effective against skin cancer.

Propranolol nanoemulgel: Preparation, in-vitro and ex-vivo characterization for a potential local hemangioma therapy

A lack of safe and effective topical alternatives to oral propranolol HCl (PHCl) hampers optimal management of infantile hemangioma (IH), particularly in complex cases with severe side effects or treatment failures. This study aimed to develop a nanoemulsion gel (NEG) for topical PHCl delivery. A meticulously formulated nanoemulsion (NE) encapsulated with clove oil, Tween 20, and polyethylene glycol 400 emerged as the standout candidate (NE3) due to its exceptional stability, resilience, and favorable drug loading. NE3 exhibited a remarkable globule size of 14.57 nm, a low polydispersity index (PDI) of 0.282, and a stabilizing zeta potential of −19.89 mV. The subsequent formulation of PHCl-NEG displayed desired rheological and spreadability properties for topical application. Ex-vivo skin retention and permeation studies revealed effective PHCl deposition within the dermal layer with minimal systemic exposure. This promising approach offers a potential alternative to oral PHCl, potentially mitigating severe side effects and improving outcomes in complex IH cases.

Formulation development and characterization of Lecarnidipine hydrochloride niosomal transdermal patches

The bioavailability of Lercanidipine Hydrochloride (LCP) is about 44% and half-life of the drug is about 4.6 hours. LCP due to its low therapeutic dose range of 2.5 to 20mg and substantial biotransformation in liver becomes it ideal molecule in development of transdermal therapeutic system. The primary objective of the present research work was to develop Niosomal transdermal patch (NP) of Lecarnidipine. The LCP nanoparticles were prepared by solvent evaporation method and the optimized Nanoparticles formulation has shown 225nm particle size with a polydispersity index (PDI) of 0.120. LCP patches were prepared by incorporating nanoparticles dispersion, using varying concentrations of polymers HPMC E5, HPMC 5cps, HPMC 15cps, Carbopol 734 and Sodium alginate using solvent casting techniques and further optimized by central composite design(CCD) the effect of polymer on the various physico-chemical characteristics and in-vitro drug release studies, ex-vivo skin permeation studies is studied. On the basis of in-vitro drug release and ex-vivo skin permeation studies, the formulation containing (HPMC 15cps and HPMC 5cps) has shown sustained and extended drug release over a period of 24 hrs.&#x0D; Keywords: Lecarnidipine; Niosomes; Transdermal patch; Central composite Design, Controlled release; Bioavailability etc.

In-Vitro and Ex-Vivo Evaluation of Transfersomal Gel of Methotrexate

Methotrexate on its oral and intravenous administration results in unwanted adverse effects. This drawback can be overcome by transdermal delivery because of its painless objective for systemic drug administration. Transfersomes are ultra-deformable vesicles with the flexibility to reach deeper tissues of the skin. The objective of this research work was to develop methotrexate transfersomal gel by thin film hydration technique, evaluated for entrapment efficiency, deformability, mean vesicle size, and stability, and incorporated into carbopol gel for ease of handling and skin applicability for a longer period of retention on skin. MTX-TFS gel & conventional gel were characterized for consistency, transparency, viscosity, and pH. Ex-vivo skin permeation studies were performed using abdominal goat skin and drug release kinetic parameters and transdermal flux were calculated using mathematical models. The results indicate that MTX was successfully entrapped (84.77 ± 2.35 %w/w) in transfersomes having 240±1.6 nm vesicle sizes and 27.13±0.7 deformability index. The gel was permeated through the skin at a rate of 28.12±2.58 µg/cm2/hr as compared to the conventional gel (10.35±2.14 µg/cm2/ hr). From the study, it was concluded that the MTX-TFS gel can be used as a possible substitute for the conventional formulation for transdermal drug delivery due to 3 times improvement in transdermal flux.

Development and characterization of amphotericin B nanoemulsion-loaded mucoadhesive gel for treatment of vulvovaginal candidiasis

Despite being recognized as the “gold standard” for treating azole-resistant vulvovaginal candidiasis, amphotericin B (AmB), an amphoteric molecule, has not been widely used due to serious issues with solubility and permeability. In light of the aforementioned, the objective of the present study was to increase AmB's therapeutic efficacy by formulating it into an o/w nanoemulsion (AmB-NE) system. Furthermore, to facilitate AmB-NE's retention within the vaginal cavity, it was loaded into a mixture of Carbopol® 974P and Aloe vera-based gel (CA gel). Briefly, in the present study, a kinetically stable batch of formulated AmB-NE having a globule size of 76.52 ± 3.11 nm, PDI of 0.342 ± 0.032, and zeta potential of -22.32 ± 0.88 mV was incorporated into the CA gel base. This AmB-NE loaded gel (AmB-NE gel) exhibited a non-Fickian/anomalous diffusion from the hydrophilic matrix. The texture analysis of AmB-NE gel revealed that the prepared gel was a non-drip, soft, easy to spread, and sufficiently cohesive gel that could reside in the vaginal cavity, which was confirmed by our ex-vivo retention test, which revealed that AmB-NE loaded gel could stay in the vaginal cavity for approximately 11 h. Ex-vivo skin permeation studies revealed that AmB-NE is 4.26 times more permeable than AmB-coarse gel, implying that AmB-NE facilitates AmB entry into the vaginal epithelial layers. Furthermore, in-vivo vaginal lavage studies revealed that AmB-NE gel permeated 7.03-fold more than AmB-coarse gel. Prepared AmB-NE gel was stable in refrigerated condition and showed no histopathological toxicity. Thus, the present study suggests that AmB-NE gel could eliminate the existing problem of AmB and that it could serve as an alternative option to treat vulvovaginal candidiasis.

Formulation and evaluation of nano structured lipid carriers for intranasal delivery of Buspirone hydrochloride

The aim of this work was to formulate buspirone hydrochloride (BH) NLCs for intranasal administration to improve BH bioavailability. The BH loaded NLCs were prepared by hot high-pressure homogenization technique using Precirol ATO 5, olive oil and tween 80 as solid lipid, liquid lipid and surfactant, respectively. Carbopol 934P and HPMC K4M were used to convert NLCs dispersion into NLCs based in-situ nasal gelling solution to improve its mucoadhesive property for intranasal administration. A factorial design approach was used to study the effect of independent variable (amount of Precirol ATO 5 and olive oil) on the dependent variables (particle size and percentage entrapment efficiency (%EE). The optimized formulation was characterized for particle size, zeta potential, %EE, and surface morphology. Fourier transform infrared (FTIR) spectroscopy was used to study the possible BH-lipid complex formation. Further, viscosity determination, stability studies, in-vitro drug release, ex-vivo skin permeation studies and ex-vivo nasal toxicity studies of BH loaded NLCs nasal gelling solution were carried out. The BH loaded NLCs (batch F8) showed particle size of 111.8nm, %EE of 78.34% and zeta potential of-44.3mV. Scanning electron microscopy (SEM) confirmed spherical shape of NLCs. In vitro drug release and ex vivo skin permeation studies of BH loaded NLCs and BH loaded NLCs in-situ nasal gelling solution showed 71.26% drug permeation.

Preparation and Evaluation of Imatinib Loaded Transfersomal gel for the Treatment of Rheumatoid Arthritis.

In the present study, imatinib-loaded transfersomal gel (imatinib-TFS-Gel) was developed to minimize the oral dosing frequency and side effects during rheumatoid arthritis (RA) therapy. Imatinib-loaded transfersomes (imatinib-TFS) were prepared by the film-hydration method. The effects of lecithin content, lecithin/ EA ratio, and the type of EA on the characteristics of the imatinib-TFS were studied using a D-optimal design. Morphology of imatinib-TFS was investigated using scanning electron microscopy. The optimized imatinib-TFS formulation was used to prepare imatinib-TFS-Gel with the aid of Carbopol 940 as the gelling agent. The Optimized imatinib-TFS had a spherical shape with the particle size of 140.53 ± 0.87 nm, polydispersity index of 0.44 ± 0.01, the zeta potential of -17.63 ± 0.65 mV, encapsulation efficiency of 98.70 ± 0.38%, and release efficiency of 81.26 ± 0.70 %. Ex-vivo skin permeation studies through the rat skin showed that the cumulative amount of imatinib permeated from imatinib-TFS-Gel was significantly higher than that from imatinib-Gel. The RA rat model indicated a substantial reduction in paw edema during the 14 days study following the application of imatinib-TFS-Gel as compared with imatinib-Gel. Therefore, imatinib-TFS-Gel can be considered as a promising drug delivery system for the treatment of RA.

Preparation of Topical Nano Gel Loaded With Hesperidin Emusomoes: In vitro and in vivo Studies

Objectives: The objective of the present study was to increase the solubility of poorly soluble drug hesperidin and to increase the efficacy of the drug by loading hesperidin in emulsomal topical gel. Methods: Hesperidin was loaded into emulsomes by using ethanol injection method. The optimized formulation of emulsomes was evaluated by SEM, FT-IR, DSC, P-XRD, in vitro drug release, ex-vivo skin permeation studies, in vivo pharmacokinetic and pharmacodynamic studies. Results: The SEM study shows the emulsomes were tiny and spherical in structure. The particle size and zeta potential of the optimized formulation was found to be 50nm and -1.8mV and in vitro drug release was found to be 98.6% for 6 hrs. The optimized emulgel was prepared by using different gelling agents Carbopol 934 and HPMC. The prepared gels were found to be homogenous and skin permeation studies was found to be 98.9% for 4 hr, with skin permeation efficacy bearing flux value 12.3μg/cm2/h when compared to the pure hesperidin gel. The in vivo pharmacokinetic and pharmacodynamic studies were found to be more efficient for the hesperidin loaded emulsomal gel when compared to the marketed formulation. Conclusion: Hesperidin emulsomal gel has shown a significant increase (p<0.05) in activity when compared to the marketed formulation.

Luliconazole loaded lyotropic liquid crystalline nanoparticles for topical delivery: QbD driven optimization, in-vitro characterization and dermatokinetic assessment

Fungal infections are an important cause of morbidity and pose a serious health concern especially in immunocompromised patients. Luliconazole (LUL) is a topical imidazole antifungal drug with a broad spectrum of activity. To overcome the limitations of conventional dosage forms, LUL loaded lyotropic liquid crystalline nanoparticles (LCNP) were formulated and characterized using a three-factor, five-level Central Composite Design of Response Surface Methodology. LUL loaded LCNP showed particle size of 181 ± 12.3 nm with an entrapment efficiency of 91.49 ± 1.61 %. The LUL-LCNP dispersion in-vitro drug release showed extended release up to 54 h. Ex-vivo skin permeation studies revealed transdermal flux value (J) of LUL-LCNP gel (7.582 μg/h/cm2) 2 folds higher compared to marketed cream (3.3706 μg/h/cm2). The retention of LUL in the stratum corneum was ∼1.5 folds higher and ∼2 folds higher in the epidermis and other deeper layers in comparison to the marketed cream. The total amount of drug penetrated (AUC0-∞) with LCNP formulation was 4.7 folds higher in epidermis and 6.5 folds higher in dermis than marketed cream. The study's findings vouch that LCNP can be a promising and effective carrier system for the delivery of antifungal drugs with enhanced skin permeation.

Improved skin-permeated diclofenac-loaded lyotropic liquid crystal nanoparticles: QbD-driven industrial feasible process and assessment of skin deposition

ABSTRACT The purpose of the present study was to optimise diclofenac diethylamine-loaded liquid crystal nanoparticles (LCNPs) using the principles of quality by design. Based on risk assessment, the effect of various formulation variables on the critical quality attributes was investigated. A three-level Box-Behnken design with 14 runs was utilised for optimisation. The LCNPs were evaluated for size, polydispersity index, zeta potential, entrapment efficiency, morphology, solid-state characterisation, and drug release. The LCNPs were found to show prolonged drug release up to 12 h as compared to the free drug which showed a 100% release in less than 3 h. The optimised formulation was further investigated for scale-up studies, incorporated into carbopol gel and characterised for rheological parameters, skin permeation, and skin accumulation. Ex-vivo skin permeation studies revealed 1.55 times more permeation as compared to the marketed formulation. The designed gel had the potential to prolong the drug release, improve the permeation of drug through the skin layers, and industrial feasibility.

Development, characterization and evaluation of nanocarrier based formulations of antipsoriatic drug “acitretin” for skin targeting

Acitretin, a 2nd generation retinoid, is a drug of choice for the treatment of severe psoriasis. Presently, only capsule formulation for oral administration is commercially available and associated with limitations of severe systemic side effects. In the present study, carrier elastic liposomal and ethosomal based topical gel formulations were developed, optimized, and characterized in-vitro, ex-vivo, and in-vivo to provide effective skin targeting of acitretin. In-vitro characterization exhibited nanometric vesicle size range (591 ± 16 and 360 ± 14 nm), high encapsulation efficacy (94.7 ± 2.1% and 91.2 ± 1.6%), optimum viscosity (1152 and 1320 cP), thixotropic behavior and good storage stability of the developed formulation. Ex-vivo skin permeation and deposition studies carried on four different biological membranes (rat, mice, porcine ear, and human cadaver skin) showed higher skin deposition of prepared carrier-based gels in comparison to plain acitretin gel. Better skin localization potential was also confirmed by mechanistic studies using Confocal Laser Scanning Microscopy and Scanning Electron Microscopy analysis. In-vivo antipsoriatic activity demonstrated the better therapeutic efficacy of carrier-based formulations. Thus, developed formulation seems to be a safe and promising alternative to oral route for effective topical delivery of acitretin with improved pharmacological activity and no systemic toxicity.

Curcumin loaded nanostructured lipid carriers for enhanced skin retained topical delivery: optimization, scale-up, in-vitro characterization and assessment of ex-vivo skin deposition

Nanostructured lipid carriers (NLC) have become a promising drug delivery system for topical delivery of drugs. Delivery of lipophilic drugs with improved stability and entrapment efficiency is one of the foremost benefits of NLC based formulations. The objective of the present study was to improve the permeation of poorly soluble curcumin into topical skin layers for the treatment of chronic inflammatory disorder psoriasis and microbial mediated acne vulgaris. Hot emulsification followed by probe sonication method was employed for the preparation of the curcumin loaded NLC. Further, in-vitro and ex-vivo characterization was performed for designed NLC. The designed NLC showed a mean particle size 96.2 ± 0.9 nm, entrapment efficiency of 70.5 ± 1.65% and zeta potential of -15.2 ± 0.566 mV. Curcumin-NLC showed extended in-vitro release upto 48 hours, whereas free curcumin showed 100% drug release within 4 hours. Ex-vivo skin permeation studies revealed 3.24 fold improved permeation and skin retention in the case of curcumin loaded NLC gel compared to free curcumin gel. The cell viability studies demonstrated the formulation components showed no toxicity towards keratinocyte cells. In keratinocyte cells, improved cell uptake was observed for curcumin-NLC compared to free curcumin dispersion. The results suggested that the NLC based formulation had potential to improve the efficacy of curcumin.

Nanocrystals of Fusidic Acid for Dual Enhancement of Dermal Delivery and Antibacterial Activity: In Vitro, Ex Vivo and In Vivo Evaluation.

With the alarming rise in incidence of antibiotic-resistant bacteria and the scarcity of newly developed antibiotics, it is imperative that we design more effective formulations for already marketed antimicrobial agents. Fusidic acid (FA), one of the most widely used antibiotics in the topical treatment of several skin and eye infections, suffers from poor water-solubility, sub-optimal therapeutic efficacy, and a significant rise in FA-resistant Staphylococcus aureus (FRSA). In this work, the physico-chemical characteristics of FA were modified by nanocrystallization and lyophilization to improve its therapeutic efficacy through the dermal route. FA-nanocrystals (NC) were prepared using a modified nanoprecipitation technique and the influence of several formulation/process variables on the prepared FA-NC characteristics were optimized using full factorial statistical design. The optimized FA-NC formulation was evaluated before and after lyophilization by several in-vitro, ex-vivo, and microbiological tests. Furthermore, the lyophilized FA-NC formulation was incorporated into a cream product and its topical antibacterial efficacy was assessed in vivo using a rat excision wound infection model. Surface morphology of optimized FA-NC showed spherical particles with a mean particle size of 115 nm, span value of 1.6 and zeta potential of −11.6 mV. Differential scanning calorimetry and powder X-ray diffractometry confirmed the crystallinity of FA following nanocrystallization and lyophilization. In-vitro results showed a 10-fold increase in the saturation solubility of FA-NC while ex-vivo skin permeation studies showed a 2-fold increase in FA dermal deposition from FA-NC compared to coarse FA. Microbiological studies revealed a 4-fofd decrease in the MIC against S. aureus and S. epidermidis from FA-NC cream compared to commercial Fucidin cream. In-vivo results showed that FA-NC cream improved FA distribution and enhanced bacterial exposure in the infected wound, resulting in increased therapeutic efficacy when compared to coarse FA marketed as Fucidin cream.

Design, Development and Delivery of Rasagiline Mesylate from Monolithic Drug in Adhesive Matrix Patches

The purpose of this research was to prepare and evaluate monolithic drug-in-adhesive type patches of Rasagiline Mesylate (RM) containing penetration enhancer and having seven day wear property. Preformulation studies like solubility in permeation enhancers, compatibility study, transmission study, uptake study and crystallization study of Rasagiline Mesylate in various pressure sensitive adhesive polymers were performed. Transdermal system was prepared by solvent casting method. The effects of various permeation enhancers (Propylene Glycol, Oleic Acid, Isopropyl Palmitate, and lauryl lactate) on the ex-vivo transcutaneous absorption of Rasagiline Mesylate through human cadaver skin were evaluated by modified Franz diffusion cell system. Ex-vivo transcutaneous absorption of prepared transdermal patch was performed using different concentration of Lauryl lactate (3%, 5%, and 7%). In-vitro Adhesion testing (Peel, tack shear etc.) was performed on different dry GSM (Grams per Square Meter) of patch like 80GSM, 100 GSM and 150 GSM. The final transdermal patches were tested for appearance, weight of matrix, thickness, % assay of drug content, in-vitro adhesion testing, cold flow study and ex-vivo skin permeation studies. Based on crystallization study and adhesion testing, Durotak-4098 (14% drug concentration) was selected as pressure sensitive adhesive. Patch containing Lauryl lactate showed highest cumulative permeation compared to other permeation enhancers. The patch containing 5% laurel lactate showed greater transdermal flux (2.36 µg/cm2 /hr). Patch with 150 dry GSM showing promising adhesion properties. Backing film Scotchpak 9723 and release liner Saint Gobain 8310 was selected based on transmission and uptake study of Rasagiline Mesylate. Stability study indicates that developed formulation remains stable. In conclusion, the present research confirms the practicability of developing Rasagiline Mesylate transdermal system.

Effect of nanostructured lipid carriers on transdermal delivery of tenoxicam in irradiated rats

Transdermal delivery of non-steroidal anti-inflammatory drugs (NSAIDs) is an effective route of drug administration, as it directs the drug to the inflamed site with reduced incidence of systemic adverse effects such as gastric hemorrhage and ulcers. Tenoxicam (TNX) is a member of NSAIDs that are marketed only as oral tablets due to very poor absorption through the skin. The current study intended to formulate and characterize a hydrogel loaded with nanostructured lipid carriers (NLCs) to enhance the transdermal delivery of TNX. Six formulations of TNX were formulated by slight modifications of high shear homogenization and ultrasonication method. The selected formula was characterized for their particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE), in-vitro drug release and ex-vivo skin permeation studies. Moreover, the effectiveness of the developed formula was studied in-vivo using carrageenan-induced paw edema and hyperalgesia model in irradiated rats. Formula F4 was chosen from six formulations, as the average diameter was 679.4 ± 51.3 nm, PDI value of about 0.02, zeta potential of −4.24 mV, EE of 92.36%, globules nanoparticles without aggregations and absence of interactions in the developed formula. Additionally, the in-vivo study showed the efficacy of formula F4 (TNX-NLCs hydrogel) equivalent to oral TNX in reducing the exaggerated inflammatory response induced by carrageenan after irradiation. In conclusion, the present findings suggest that TNX-NLCs hydrogel could be a potential transdermal drug delivery system alternative to the oral formulation for the treatment of various inflammatory conditions.

DEVELOPMENT AND EVALUATION OF NANOPARTICLES BASED TRANSDERMAL PATCH OF AGOMELATINE FOR THE TREATMENT OF DEPRESSION

Agomelatine (AGM) is an antidepressant drug. Its extensive hepatic first-pass metabolism coupled with low biological half-life shows 5% absolute bioavailability on oral administration. Polymeric nanoparticles (PNPs) have capability to efficiently penetrate the skin barrier and BBB so as to effectively reach the drug to site of action. Polymeric nanoparticles of drug (AGM-PNPs) with PLGA polymer were prepared by nanoprecipitation method followed by solvent evaporation. The particle size, polydispersity index, zeta potential and % entrapment efficiency of the optimized formulation were found to be compliant with the desired standards. DSC, FT-IR and XRD methods of instrumental analysis confirmed the formation of AGM-PNPs. Matrix–type transdermal patch containing AGM-PNPs (formulation TP 2) and AGM (formulation TP 1) were prepared by a solvent evaporation method using a film former machine. In-vitro drug release from patch formulations TP1 and TP2 were found to be 47.41 ± 1.78 and 70.16 ± 1.74. The drug release data of the in-vitro drug release study was analysed with kinetic models zero order, first order release kinetic model, Higuchi model, Korsmeyer-peppas model. In ex-vivo skin permeation studies, transdermal patch formulation containing AGMPNPs (TP 2) shown least lag time as compared to transdermal patch containing agomelatine (TP-1).

FORMULATION AND OPTIMIZATION OF QUERCETIN LOADED NANOSPONGES TOPICAL GEL: EX VIVO, PHARMACODYNAMIC AND PHARMACOKINETIC STUDIES

Objective: Quercetin is therapeutically hampered because of its poor solubility. The present investigation was aimed to prepare quercetin loaded nanosponges topical gel to enhance the solubility and efficacy of the drug.&#x0D; Methods: Quercetin nanosponges were prepared by emulsion solvent diffusion method. Developed nanosponges optimized by particle size, SEM, entrapment efficiency, FT-IR, DSC, P-XRD, In vitro studies. The optimized formulation of nanosponges was loaded into a topical gel and it was characterized by ex-vivo, in vivo Pharmacodynamic and kinetic studies.&#x0D; Results: The particle size and zeta potential of optimized nanosponges were found to be 188.3 nm and-0.1mV. Surface morphology was studied using SEM Analysis which showed tiny sponge-like structure and entrapment efficiency was found to be 96.5 %. In vitro drug release of optimized nanosponges was found to be 98.6% for 7hours. Optimized nanosponges entrapped gel was prepared by using carbopol 934 and hydroxypropyl methylcellulose as gelling agents. The prepared nanogels were homogenous and ex-vivo skin permeation studies of the optimized nanosponges gel was found to be 98.1% for 5 h, quercetin loaded nanosponges has shown higher skin permeation efficiency (18.4µg/cm2±2.1) compared to pure quercetin gel. The pharmacokinetic and pharmacodynamic studies showed that the quercetin loaded nanosponges has shown more effective when compared to marketed formulation.&#x0D; Conclusion: Quercetin loaded nanosponges gel has shown a significant increase in activity (p&lt;0.05) compared to the marketed formulation (Voveran Emulgel).