Ex-vivo Permeation Studies Research Articles

FORMULATION AND CHARACTERISATION OF RISEDRONATE SODIUM SUBLINGUAL SPRAY

Objective: To formulate a propellant-free sublingual spray of Risedronate sodium, addressing issues of gastrointestinal side effects associated with current oral formulations and improving patient compliance. Methods: Initially, a fractional factorial design was used to screen variables, followed by a face-centered central composite design for optimization. Formulation batches were characterized by spray pattern, spray angle, leak test, prime test, drug delivery uniformity, drug content per spray, and ex-vivo permeation study. Results: The optimized batch O1 exhibited an ovality ratio of 1.1, a spray angle of 640, and a drug permeation percentage of 4. In vivo absorption analysis revealed that the relative bioavailability of optimized batch O1 was 2.27 times higher than that of the plain drug solution. Compatibility of the product pack with excipients and the drug was confirmed through stability studies of batch O1. Conclusion: The study concluded that Risedronate sodium sublingual spray presents a promising alternative to oral administration, potentially reducing gastrointestinal side effects and enhancing patient compliance.

Enhanced Transdermal Delivery of Cilnidpine Via Ultradeformable Vesicle Loaded Patch: Statistical Optimization, Characterization and Pharmacokinetic Assessment.

The study aimed to address the limitations of oral delivery and enhance the bioavailability of Cilnidipine (often prescribed as antihypertensive drug) (CND) through the development of transdermal patches containing ultra-deformable transferosomes. CND, known for its low oral bioavailability and adverse effects, was encapsulated in transferosomes using a thin film hydration method. Seventeen formulations were made (using Box Behnken Design), varying Soya lecithin, Tween-80, and rotary evaporator's speed, and evaluated for vesicle size, polydispersity index (PDI), and entrapment efficiency (EE %). The better formulation was selected based on these parameters and incorporated into transdermal patches. Physicochemical properties, in-vitro and ex-vivo permeation, and skin irritancy studies were conducted on the patches. Pharmacokinetic studies were conducted using male Wistar albino rats. The study found that the developed transferosomal formulations had vesicle sizes between 185 nm and 401 nm, entrapment efficiency (EE%) between 63% and 92%, and zeta potential ranging from -52 mV to -20 mV. Both in-vitro and ex-vivo permeation studies showed that transferosomal formulations provided significantly better drug permeation than plain Cilnidipine patches, with increased permeation linked to higher PEG-400 concentrations. The transferosomal patches did not cause skin irritation. The optimized formulation exhibited a higher % drug release (85.7±1.5%). In pharmacokinetic studies using male Wistar albino rats, the transferosomal patch CTP-17 demonstrated a higher maximum concentration (Cmax) of 1565.068 mcg/ml and a greater area under the curve (AUC) of 13225.352 μg h/ml compared to oral administration. The study concludes that the transferosomal patches of CND offer a promising approach for effective transdermal delivery, potentially improving hypertension management for prolonged periods in a controlled manner.

Formulation and Optimization of Solid Lipid Nanoparticle-based Gel for Dermal Delivery of Linezolid Using Taguchi Design.

Linezolid (LNZ) is a synthetic oxazolidinone antibiotic approved for the treatment of uncomplicated and complicated skin and soft tissue infections caused by gram-positive bacteria. Typically, LNZ is administered orally or intravenously in most cases. However, prolonged therapy is associated with various side effects and life threatening complications. Cutaneous application of LNZ will assist in reducing the dose, hence minimizing the unwanted side/adverse effects associated with oral administration. Dermal delivery provides an alternative route of administration, facilitating a local and sustained concentration of the antimicrobial at the site of infection. The current research work aimed to formulate solid lipid nanoparticles (SLNs) based gel for dermal delivery of LNZ in the management of uncomplicated skin and soft tissue infections to maximise its benefits and minimise the side effects. SLNs were prepared by high-shear homogenisation and ultrasound method using Dynasan 114 as solid lipid and Pluronic F-68 as surfactant. The effect of surfactant concentration, drug-to-lipid ratio, and sonication time was investigated on particle size, zeta potential, and entrapment efficiency using the Taguchi design. The main effect plot of means and signal-to-noise ratio were generated to determine the optimized formulation. The optimized batch was formulated into a gel, and ex-vivo permeation study, in-vitro and in-vivo antibacterial activity were conducted. The optimised process parameters to achieve results were 2% surfactant concentration, a drug-to-lipid ratio of 1:2, and 360 s of sonication time. The optimized batch was 206.3± 0.17nm in size with a surface charge of -24.4± 4.67mV and entrapment efficiency of 80.90 ± 0.45%. SLN-based gel demonstrated anomalous transport with an 85.43% in vitro drug release. The gel showed a 5 cm zone of inhibition while evaluated for in vitro antibacterial activity against Staphylococcus aureus. Ex-vivo skin permeation studies demonstrated 20.308% drug permeation and 54.96% cutaneous deposition. In-vivo results showed a significant reduction in colony-forming units in the group treated with LNZ SLN-based gel. Ex-vivo studies ascertain the presence of the drug at the desired site and improve therapy. In-vivo results demonstrated the ability of SLN-based gel to significantly reduce the number of bacteria in the stripped infection model. The utilization of SLN as an LNZ carrier holds significant promise in dermal delivery.

Assessing the Efficacy of Berberine Hydrochloride-loaded Transethosomal Gel System in Treating Dermatophytosis Caused by Trichophyton rubrum in ex-vivo, in-vitro and in-vivo Models.

Dermatophytosis is the most common dermatological disorder worldwide. Many drugs are available in the market for the treatment of dermatophytosis, but they have had limited success due to the stratum corneum barrier, antifungal resistance, drug permeation, drug retention in skin layers, etc. Thus, there is a constant need for new topical compounds that are effective against dermatophytosis. Berberine-hydrochloride is an attractive candidate to become an antifungal drug, and by using nanotechnology, it achieves deeper penetration in skin layers with enhanced permeability through the stratum corneum. In this study, we developed an oleic acid-containing berberine-hydrochloride-loaded transethosomal gel for effective treatment of dermatophytosis by Trichophyton rubrum. Berberine- hydrochloride-loaded transethosomal gels were fabricated using the hot homogenization method, followed by the incorporation of transethosomes into the gel-based system using carbopol 934. Transethosomal gel was characterized by physicochemical properties, in vitro drug release, ex-vivo permeation studies, CLSM visualization, antifungal activity, histopathological evaluation, and dermatokinetic study. Berberine-hydrochloride-loaded transethosomes seemed to be spherical and found in a range between 200-300 nm. Berberine-hydrochloride-loaded transethosomal gel formulation also exhibited controlled ex-vivo permeation of berberine-hydrochloride over 24 hr through excised rat skin, and CLSM confirmed deeper penetration into skin layers. The in vivo study revealed that transethosomal gel had a healing effect on the skin of Wistar rats infected with Trichophyton rubrum and was better than luliconazole cream. The histopathological evaluation confirmed its safety, and the dermatokinetic study showed transethosomal gel superiority over marketed cream. Therefore, the incorporation of berberine hydrochloride-loaded transethosomal nanosystems into the gel has the potential to enhance antifungal activity and permeation through transdermal drug delivery.

A macromolecule infliximab loaded reverse nanomicelles-based transdermal hydrogel: An innovative approach against rheumatoid arthritis

Infliximab (IFX) is used as a biotherapeutic agent for the treatment of rheumatoid arthritis (RA); however, its biological activity is lost orally because of variations in gastric pH and enzymatic degradation, and reduced bioavailability. The authors have tried to improve the efficacy of macromolecule delivery through transdermal route. Polycaprolactone-Polyethylene glycol-Polycaprolactone (PCL-PEG-PCL) triblock copolymer previously synthesized and was used as an efficient carrier for the preparation of IFX loaded reverse nanomicelles (IFX-RNMs). The RNMs were fabricated via nanoprecipitation technique, characterized and then were incorporated into a Carbopol-based hydrogel with eucalyptus oil (EO) as a penetration enhancer. The optimized RNMs had a particle size of 72.32 nm and an encapsulation efficiency of 83 %. In vitro release, exhibited a sustained pattern of IFX from the prepared carrier system, ex-vivo skin permeation and fluorescence microscopic studies revealed that IFX-RNMs loaded hydrogel with EO markedly improved permeation. An in vivo study was carried out on a CFA-induced RA mice model that revealed significant improvements in the results of behavioral parameters, biochemical assays, histopathological and radiological analysis. Overall, the results concluded that the IFX-RNMs loaded hydrogel can be used as a suitable approach for treating RA.

Application of Box-Behnken Design for Formulation Optimization of Sorafenib loaded Nanoparticles Targeting to Liver Carcinoma: Ex-vivo Intestinal Permeation and Cytotoxicity Study.

The anticancer drug sorafenib (SFB) was formulated as a polymeric nanoparticle using Box-Behnken design. The solvent evaporation method was utilized to develop the sorafenib polymeric nanoparticles. Formulations were then evaluated in terms of their morphological structure, entrapment efficiency (EE%), zeta potential, polydispersity index (PDI), and particle size. Ex-vivo intestinal permeation studies for pure drugs, as well as optimized formulation, were performed in rats. Furthermore, the anticancer activity was evaluated using the HepG2 cancer cell lines. Transmission electron microscopy (TEM) revealed that the improved formulation had a particle size of 175 nm, PDI of 0.134, zeta-potential of -23.8 mV, and the sorafenib-loaded PLGA NP were recognized as spherical particles. Over 90% of the drug was released in less than 24 hours, with an EE% of 85.1%. Sorafenib-loaded PLGA NP efficiently inhibited HepG2 cells.

Box-Behnken Design Optimization of Captopril-Loaded Transferosomes: Formulation and Characterization.

This study aimed to overcome the limitations of oral delivery and enhance the permeation of Captopril (CPL) by developing transferosomes. Transferosomes encapsulating CPL were prepared using a thin film hydration method. Seventeen formulations were prepared, varying Soya lecithin, Tween-20, and sonication speed. The formulations were evaluated for vesicle size (VS), polydispersity index (PDI), and entrapment efficiency (EE%). The optimized formulation’s discharge profile was compared with that of the CPL suspension. Transferosomes exhibited VS ranging from 244 to 376 nm and EE% from 65 to 91%, with zeta potentials ranging from -51 to -26 MV. In-vitro and ex-vivo permeation studies demonstrated superior drug permeation for transferosomal formulations compared to plain CPL suspension. CPL transferosomes represent a promising delivery system for prolonged and controlled drug discharge, offering potential improvements in hypertension management.

Development and Evaluation of Voriconazole Loaded Invasomes Gel for Enhanced Antifungal Activity.

Although it has limited solubility and poor permeability to the skin, voriconazole (VRC) is a viable choice for the topical treatment of fungal infections. Owing to these constraints, treating the inflection requires several injections over an extended period. The goal of this work was to produce a VRC invasome gel with improved topical antifungal activity. The Box-Behnken design (BBD) program was utilized to optimize the IVS after it was created using the thin-film hydration process. The optimized invasome formulation through BBD has 159.9 nm of vesicle size, 68.58% of entrapment efficiency, and 23.5 mV of zeta potential. The spherical shape of the vesicle was revealed using scanning microscopy. According to FTIR spectra, the medication and polymers do not interact. The optimized invasomal VRC gel exhibited an optimum of 345 to 589 cp. Ex-vivo permeation studies of IG4 exhibited a higher flux of 0.168 as compared to pure voriconazole. An antimicrobial study was accepted to check the antimicrobial efficiency of voriconazole gel (IG4). The study confirmed a good zone of inhibition of the fungus infection (C. albicans). The voriconazole invasome’s potential diffusion and antibacterial efficacy are demonstrated here. Invasomal gel was found to be an effective carrier and a desirable strategy for improving the topical distribution of VRC to treat fungal infections.

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.

Kojic Acid Containing Novel Drug Delivery System on Facial Dyschromia: Characterization and Their Evaluation

Stubborn skin pigmentation issues like post-inflammatory hyperpigmentation (PIH) and melasma are the primary reasons people seek cosmetic consultations. Treating these conditions topically is challenging, as it involves inhibiting various stages of production of the pigment process. A powerful tyrosinase inhibitor like, kojic acid (KA) is employed as a formulation to regulate pigmentation production by suppressing the melanogenesis process. It’s important to note that the application of KA has been approved by the Food and Drug Administration (FDA), US, for dermatological treatments. The goal of this investigation was to formulate a nanoemulsion containing kojic acid for skin delivery using an emulsification method. The characteristics of the KA nanoemulsion were thoroughly examined through techniques like fourier transform infrared spectroscopy, (FTIR) particle size analysis and transmission electron microscopy (TME). In addition, the formulation’s performance was evaluated through both ex-vivo permeation study and in-vitro release study. Analysis of the FTIR, X-ray diffraction (XRD), and differential scanning calorimetry (DSC) results revealed that kojic acid with other ingredients in the formulation did not exhibit any chemical interactions. The kojic acid nanoparticles that were produced exhibited a spherical shape and were uniformly distributed, with an average size diameter of 184 nm. In in-vitro tests, it was observed that 87.67% of the drug was released within 12 hours. Moreover, ex-vivo permeation evaluation demonstrated that 81.24% of the drug permeated the skin within 8 hours of application. The thermal stability studies confirmed the stability of the kojic acid nanoemulsion, with no signs of creaming, cracking, or phase separation in the formulation. In conclusion, the findings of this study suggest that the kojic acid nanoemulsion holds great promise as an effective means for delivering kojic acid within the upper layers of the skin for treating of facial dyschromia.

The Smart Drug Delivery of Rotigotine Using Transdermal Patch for the Successful Management of Parkinson's Disease.

A Non-Ergot Dopamine Agonist (NEDA) rotigotine has been designed as a new transdermal drug delivery system. To maintain optimum homogeneity in drug content, the rotigotine transdermal patch was developed utilizing a solvent casting technique. The characteristics of a transdermal patch, including patch weight, folding endurance, patch thickness, surface morphology, tensile strength, swelling rate, surface pH, in vitro release studies, water retention rate, uniformity of drug content, and ex-vivo permeation studies, were determined. In vitro drug release studies unequivocally demonstrated that drug release controlled polymer interactions. There was no apparent lag period before the drug release rate started to decline. The developed patch showed 70 ± 1.18 % of prolongation of drug release within 24 hours. The result of the penetration studies demonstrated that 61 ± 2.52% of rotigotine permeated through the epidermal barrier within 24 h. The developed transdermal patch comprising rotigotine was evidently placed on the dermis layer, and an appropriate dose was delivered into circulation for a longer time based on the aforementioned factors. The findings of this study illustrate the effective approach of transdermal patches to treat Parkinson's disease.

Novel composite fatty acid vesicles-in-Pluronic lecithin organogels for enhanced magnolol delivery in skin cancer treatment

A novel composite carrier composed of Pluronic lecithin organogels and fatty acid vesicles was used to enhance the stability and facilitate the topical delivery of a natural bioactive drug, magnolol (Mag), for treatment of skin cancer. Jojoba oil was incorporated in the organogel (OG) base to provide a synergistic effect in treatment of skin cancer. The organoleptic properties, rheological behavior, morphology, and drug content of the OG formulations were investigated with emphasis on the impact of vesicle loading on the OG characteristics. The effect of OG on Mag release and ex-vivo permeation studies were evaluated and compared to free Mag in OG. The biological anti-tumor activity of the OG formulae was assessed using a skin cancer model in mice.All OG formulations exhibited uniform drug distribution with drug content ranging from 92.22 ± 0.91 to 100.45 ± 0.77 %. Rheological studies confirmed the OG shear-thinning flow behavior. Ex-vivo permeation studies demonstrated that the permeation of Mag from all OG formulations surpassed that obtained with free Mag in the OG. The anti-tumor activity studies revealed the superior efficacy of 10-hydroxy-decanoic acid (HDA)-based vesicles incorporated in OG formulations in mitigating 7,12- dimethylbenz(a)anthracene (DMBA)-induced skin cancer, thereby offering a promising platform for the local delivery of Mag.

Chitosan films synthesized via thiol-ene click chemistry: Toward safe and versatile platforms for packaging, cosmetics and biomedical applications

The first synthesis of chitosan-based films using bio-based reticulating agents via Thiol-Michael addition click reaction was described, along with their successful application in packaging, cosmetics, and biomedical fields. The impact of chitosan (CS) concentration and the type of synthesized bio-sourced biacids (GD) and triacids (GT and TT) on the physicochemical properties of these films were assessed. Films prepared with dibasic and tribasic acids (4%-CS) demonstrated superior mechanical properties and lower solubility compared to those containing 2% CS. The incorporation of the bio-sourced GD, GT, and TT acids led to a reduction of 53%, 60% and 60.4%, respectively, in the water vapor permeability (WVP) of 4% CS-based films compared to the control film. Remarkably, CS-TT-4% films exhibited the highest mechanical strength (TS), elongation at break (%E), elasticity, water vapor, and light barrier properties. Cytotoxicity tests performed on the NIH 3T3 fibroblast cell line showed that CS-GD-4% films exhibited the highest compatibility. The efficiency of these films as drug carriers was tested with challenging anticancer and cosmetic molecules, particularly etoposide (ETP) caffeine (Caf), showing very high drug loading with a progressive release of less than 20% after 72h of incubation. Moreover, ex-vivo permeation studies in rat skin revealed that the percutaneous absorption of Caf is significantly increased by a factor of 5.5 compared to that of CS-GD-4%-Caf films with no significant histological alterations of skin layers. Altogether, this work evidences the most suitable casting solvent for developing safe chitosan films, promising their potential applications in the cosmetic and biomedical fields.

Transcutaneous Delivery of Dexamethasone Sodium Phosphate Via Microneedle-Assisted Iontophoretic Enhancement - A Potential Therapeutic Option for Inflammatory Disorders.

This study aimed to fabricate dexamethasone sodium phosphate loaded microneedle arrays (MNA) and investigate their efficiency in combination with iontophoresis for the treatment of hind paw oedema in rats. Drug loaded polyvinyl alcohol, polyvinyl pyrrolidone and D-sorbitol-based MNA11 were fabricated by vacuum micromolding. Physicochemical, morphological, thermal, in-silico, in-vitro insertion ability (on parafilm) and drug release studies were performed. Ex-vivo permeation, in-vivo insertion and anti-inflammatory studies were performed in combination with iontophoresis. MNA11 displayed sharp-tipped projections and acceptable physicochemical features. Differential scanning calorimetry results indicated that drug loaded MNA11 were amorphous solids. Drug interacted with PVP and PVA predominately via hydrogen bonding. Parafilm displayed conspicuously engraved complementary structure of MNA11. Within 60min, 91.50 ± 3.1% drug released from MNA11. A significantly higher i.e., 95.06 ± 2.5% permeation of drug was observed rapidly (within 60min) from MNA11-iontophoresis combination than MNA11 i.e., 84.07 ± 3.5% within 240min. Rat skin treated using MNA11 and MNA11-iontophoresis showed disruptions / microchannels in the epidermis without any damage to underlying anatomical structures. MNA11-iontophoresis combination led to significant reduction (83.02 ± 3.9%) in paw oedema as compared to MNA11 alone (72.55 ± 4.1%). MNA11-iontophoresis combination can act as a promising candidate to deliver drugs transcutaneously for treating inflammatory diseases.

Oral In-Situ Nanoplatform with Balanced Hydrophobic-Hydrophilic Property for Transport Across Gastrointestinal Mucosa.

Transport of oral nanocarriers across the GI epithelium necessitates transport across hydrophilic mucus layer and the hydrophobic epithelium. Based on hydrophobic-hydrophilic balance, Curcumin-Lipomer (lipid-polymer hybrid nanoparticles) comprising hydrophobic stearic acid and hydrophilic Gantrez™ AN 119 (Gantrez) were developed, by a radical in-situ approach, to successfully traverse both barriers. A monophasic preconcentrate (Cur-Pre) comprising Cur(Curcumin), stearic acid, Gantrez and stabilizers, prepared by simple solution, was added to an aqueous phase to instantaneously generate Curcumin-Lipomer (Cur-Lipo) of nanosize and high entrapment efficiency (EE). Cur-Lipo size and EE was optimized by Box-Behnken Design. Cur-Lipomers of varying hydrophobic-hydrophilic property obtained by varying the stearic acid: Gantrez ratio exhibited size in the range 200-400nm, EE > 95% and spherical morphology as seen in the TEM. A decrease in contact angle and in mucus interaction, evident with increase in Gantrez concentration, indicated an inverse corelation with hydrophilicity, while a linear corelation was observed for mucopenetration and hydrophilicity. Cur-SLN (solid lipid nanoparticles) which served as the hydrophobic reference revealed contact angle > 90°, maximum interaction with mucus and minimal mucopenetration. The ex-vivo permeation study through chicken ileum, revealed maximum permeation with Cur-Lipo1 and comparable and significantly lower permeation of Cur-Lipo1-D and Cur-SLN proposing the importance of balancing the hydrophobic-hydrophilic property of the nanoparticles. A 1.78-fold enhancement in flux of hydrophobic Cur-SLN, with no significant change in permeation of the hydrophilic Cur-Lipomers (p > 0.05) following stripping off the mucosal layer was observed. This reiterated the significance of hydrophobic-hydrophilic balance as a promising strategy to design nanoformulations with superior permeation across the GI barrier.

P-gp inhibition and enhanced oral bioavailability of amikacin Sulfate: A novel approach using Thiolated Chito-PEGylated Lipidic Hybrids

This study aimed to develop oral lipidic hybrids of amikacin sulfate (AMK), incorporating thiolated chitosan as a P-glycoprotein (P-gp) inhibitor to enhance intestinal absorptivity and bioavailability. Three formulations were designed: PEGylated Liposomes, Chitosan-functionalized PEGylated (Chito-PEGylated) Lipidic Hybrids, and Thiolated Chito-PEGylated Lipidic Hybrids. The physical characteristics of nanovesicles were assessed. Ex-vivo permeation and confocal laser scanning microscopy (CLSM) studies were conducted to evaluate the formulations’ potential to enhance AMK intestinal permeability. In-vivo pharmacokinetic studies in rats and histological/biochemical investigations assessed the safety profile and oral bioavailability. The AMK-loaded Thiolated Chito-PEGylated Lipidic Hybrids exhibited favorable physical characteristics, higher ex-vivo permeation parameters, and verified P-gp inhibition via CLSM. They demonstrated heightened oral bioavailability (68.62% absolute bioavailability) and a sufficient safety profile. Relative bioavailability was significantly higher (1556.3% and 448.79%) compared to PEGylated Liposomes and Chito-PEGylated Lipidic Hybrids, respectively, indicating remarkable oral AMK delivery with fewer doses, reduced side effects, and enhanced patient compliance.

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.

Impact of Penetration Enhancer and Natural Oil on Transdermal Delivery of Modified Karaya Gum Gel

The etodolac based modified karaya gum (MKG) gel was developed using 32 factorial design to enhance the therapeutic effect of gel to treat inflammation. Gels were prepared with different concentrations of MKG and arachis oil using 32 factorial design. The percentage of drug content was found in the range of 96 to 99%, viscosity results shown in the range of 842 CPS to 2560 CPS and in vitro drug release was found to be in range of 38% to 98% respectively. Whereas ex-vivo permeation studies of etodolac gel and pure etodolac solution across the burned pig skin were shown 72% and 42% respectively. The drug and excipient compatibility studies by FTIR confirms that, there is no major functional group change was observed. The results concluded that, the combination of MKG and arachis oil were improved the penetration of etodolac through burned pig skin thereby the combination of PE and oil successfully enhanced the therapeutic effect of etodolac.

BBD assisted in-situ nanoliposomes of esculin hydrate via intranasal delivery for the amelioration of Parkinson's disease

The objective of this research was to develop and optimise esculin Hydrate loaded nanoliposomes (ESH-NLs). The nanoliposomes were prepared by solvent evaporation method and optimized using a three-factor, three-level Box-Behnken design. Phospholipid 90G (X1), cholesterol (X2), and sonication time (X3) were used as independent variables, and their effects on vesicle size (Y1), entrapment efficiency (Y2), and Polydispersity index (Y3) were observed. The opt-ESH-NLs were further characterised for in-vitro drug release, DPPH assay, confocal laser scanning microscopy, and ex-vivo permeation. Opt-ESH-NLs had a vesicle size of 88.36 nm, a PDI of 0.06, an entrapment efficiency of 94.22 ± 0.93 %, and a drug release of 76.776 ± 1.127 %. Compared to standard ascorbic acid, the antioxidant activity was found to be 78.52 ± 0.148 %. Ex-vivo permeation studies revealed that opt-ESH-NLs had significantly enhanced permeation (79.484 ± 0.754 %) compared to ESH suspension (38.326 ± 1.279 %). Pharmacokinetic study revealed that opt-ESH-NLs when compared with Oral ESH suspension had a significant bioavailability in Brain as compared to plasma. The stability study of nanoliposomes at 4 °C reveals there is no significant change in the formulation. It was concluded that opt-ESH-NLs is a promising and effective formulation for intranasal administration for direct delivery of drug in the brain for amelioration of PD.