Pure Drug Solution Research Articles

Comparison of Pharmacokinetic Characteristics of Bilosomal Dispersion Versus Pure Solution of Oral Ropinirole Hydrochloride in Rats

Background: Ropinirole hydrochloride is a non-ergoline antiparkinson drug. It is a highly hydrophilic drug and classified as class III according to Biopharmaceutical Classification System with low absolute oral bioavailability of approximately 50% upon oral administration due to significant hepatic first-pass metabolism. Objective: to compare the pharmacokinetic parameters of Ropinirole, when administered orally in the form of a Ropinirole bilosomal dispersion in contrast to an oral Ropinirole solution. Methods: This study involved the use of twelve male Wistar rats, with an average weight of 220±11 g, and these rats were divided into two groups, comprising six rats each. A 1.1mg/kg doses of pure Ropinirole and Ropinirole bilosomes were administered orally through gavage after reconstituting in distilled water. Ropinirole was quantified in the rat's plasma using HPLC, subsequently establishing a spiked calibration curve with plasma samples and utilizing paracetamol as an internal standard. The statistics included mean values (± SD; n = 6) for pharmacokinetic parameters, with statistical significance assessed using a Student's t-test. Results: For the oral bilosomes, the values were 9.4±0.11 μg /ml for Cmax, 3±0.00 h for Tmax, and 55.56±2.12 μg h/ml for AUC0-24. In contrast, for the oral solution, the corresponding values were 7.2±0.14 μg/ml for Cmax, 1.5±0.00 h for Tmax, and 23.70±2.23 μg h/ml for AUC0-24. These parameters were significantly higher (P<0.05) as compared with a pure drug solution. The comparative bioavailability of Ropinirole (AUC0-24 oral solution / AUC0-24 oral bilosomes ) is equal to 42.66%, which indicates the bioavailability of the oral RH solution was less than that of RH bilosomal dispersion. Conclusions: The use of nano vesicular carriers (bilosomes) shows significant potential as an effective delivery system for improving the oral bioavailability of ropinirole hydrochloride

Propellant Free Pressurized Spray System of Etodolac to Manage Acute Pain Conditions: In Vitro and In Vivo Evaluation.

This study aimed to develop a propellant-free topical spray formulation of Etodolac (BCS-II), a potent NSAID, which could be beneficial in the medical field for the effective treatment of pain and inflammation conditions. The developed novel propellant-free spray formulation is user-friendly, cost-effective, propellant-free, eco-friendly, enhances the penetration of Etodolac through the skin, and has a quick onset of action.Various formulations were developed by adjusting the concentrations of different components, including lecithin, buffering agents, film-forming agents, plasticizers, and permeation enhancers. The prepared propellant-free spray formulations were then extensively characterized and evaluated through various in vitro, ex vivo, and in vivo parameters. The optimized formulation exhibits an average shot weight of 0.24 ± 0.30ml and an average drug content or content uniformity of 87.3 ± 1.01% per spray. Additionally, the optimized formulation exhibits an evaporation time of 3 ± 0.24min. The skin permeation study demonstrated that the permeability coefficients of the optimized spray formulation were 21.42cm/h for rat skin, 13.64cm/h for mice skin, and 18.97cm/h for the Strat-M membrane. When assessing its potential for drug deposition using rat skin, mice skin, and the Strat-M membrane, the enhancement ratios for the optimized formulation were 1.88, 2.46, and 1.92, respectively against pure drug solution. The findings from our study suggest that the propellant-free Etodolac spray is a reliable and safe topical formulation. It demonstrates enhanced skin deposition, and improved effectiveness, and is free from any skin irritation concerns.

Fabrication and in vitro–in vivo evaluation of ligand appended isoniazid loaded nanoparticulate systems for the treatment of tuberculosis

Isoniazid (INH) is amongst the first-line antibiotics that have been employed for the treatment of Tuberculosis (TB). Despite its potent anti-tubercular action, susceptibility to rapid hepatic first-pass metabolism and elimination largely limits its oral bioavailability, and has been associated with the induction of drug resistance and adverse effects. This presents study aims at the development and evaluation of unique mannosylated INH loaded solid lipid nanoparticles (Mn-INH-SLNs) for the treatment of TB. The Mn-INH-SLNs demonstrated a particle size of 466 ± 11 nm, which was acceptable for macrophage targeting and had % entrapment efficiency of 80.41 ± 1.37% (n = 6). The dissolution studies depicted a dual-phase drug release profile, i.e., burst release followed by a sustained release, revealing the best fit with the Korsmeyer-Peppas model. The MTT assay (cytotoxicity study) performed utilizing J774A.1 cells with optimized Mn-INH-SLNs deemed them to be safe and nontoxic. Mannosylated SLNs tagged with coumarin-6 (C6 – an established fluorescent marker) showed a substantially high intracellular internalization (1.11-folds) when analyzed through flow cytometric analysis (FACS). The in vivo pharmacokinetic evaluation following per-oral administration in rats demonstrated a significant rise in relative bioavailability (∼5.5-folds) with Mn-INH-SLNs compared to pure drug solution. The bio-distribution (drug disposition) studies exhibited greater lung accumulation of Mn-INH-SLNs (2.13-folds) in comparison to the unconjugated INH-SLNs (Un-INH-SLNs). The promising results of the study depict that the targeted-optimized Mn-INH-SLNs may be a propitious and potent tool to fight TB.

Fabrication and in vitro characterization of curcumin film-forming topical spray: An integrated approach for enhanced patient comfortandefficacy.

Curcumin, known for its anti-inflammatory properties, was selected for the developing consumer friendly film forming spray that offers precise delivery of curcumin and and improves patient adherence. An optimized film-forming solution was prepared by dissolving curcumin (1%), Eudragit RLPO (5%), propylene glycol (1%), and camphor (0.5%) in ethanol: acetone (20:80) as the solvent. The solution was filled in a spray container which contained 70% solutions and 30% petroleum gas. In-vitro characterization was performed. Potential anti-inflammatory phytoconstituents were extracted from the PubChem database and prepared as ligands, along with receptor molecules (nsp10-nsp16), for molecular docking using Autodock Vina. The docking study showed the lowest binding energy of -8.2 kcal/mol indicates better binding affinities. The optimized formulation consisted of ethanol:acetone (20:80) as the solvent, Eudragit RLPO (5%) as the polymer, propylene glycol (1%) as the plasticizer, and camphor oil (0.5%) as the penetration enhancer. The optimized formulation exhibited pH of 5.8 ± 0.01, low viscosity, low film formation time (19.54 ± 0.78 sec), high drug content (8.243 ± 0.43 mg/mL), and extended ex vivo drug permeation (85.08 ± 0.09%) for nine hours. Consequently, the formulation was incorporated into a container using 30% liquefied petroleum gas, delivering 0.293 ± 0.08 mL per actuation, containing 1.53 ± 0.07 mg of the drug. The film-forming spray exhibited higher cumulative drug permeation (83.94 ± 0.34%) than the marketed cream formulation and pure drug solution after 9 h, with an enhancement ratio of 14. Notably, the film-forming spray exhibited no skin irritation and remained stable for over three months. The developed curcumin film-forming system is promising as a carrier for wound management because of its convenient administration and transport attributes. Further in vivo studies are required to validate its efficacy in wound management.

Formulation, Optimization, and Evaluation of Gliclazide loaded Nanosuspension for Dissolution Rate Enhancement

Diabetes mellitus is a prolonged metabolic condition categorized through elevated blood glucose levels. To treat this condition, oral antihyperglycemic medications like gliclazide, a second-generation sulfonylurea insulin secretagogue, are commonly used. Gliclazide comes into the biopharmaceutical classification system (BCS) class-II types, known for its lower solubility. To enhance its solubility, gliclazide was integrated into nanosuspensions. This study focused on formulating these gliclazide nanosuspensions using Kollicoat IR and Soluplus through the anti-solvent-precipitation method, through optimization achieved using the Box Behnken Design. Key parameters assessed included particle size (224 ± 1.23 nm) and entrapment efficiency (95.65 ± 0.12%). The drug release studies conducted on pH 7.4 indicated that over 95% of the drug was released within 30 minutes for the nanosuspension, whereas the pure drug solution released less than 70% in the same time frame, indicating immediate release with the nanosuspension. The morphology was examined using scanning electron microscopy (SEM), while fourier transform infrared (FTIR), X-Ray diffractometers (XRD), and differential scanning calorimeter (DSC) analyses confirmed the presence of the drug within the nanosuspension. In summary, the incorporation of gliclazide into nanosuspensions proved successful, resulting in enhanced release characteristics and ameliorated solubility.

Mannose-Functionalized Isoniazid-Loaded Nanostructured Lipid Carriers for Pulmonary Delivery: In Vitro Prospects and In Vivo Therapeutic Efficacy Assessment.

Resistance to isoniazid (INH) is common and increases the possibility of acquiring multidrug-resistant tuberculosis. For this study, isoniazid-loaded nanostructured lipid carriers (INH-NLCs) were developed and effectively functionalized with mannose (Man) to enhance the residence time of the drug within the lungs via specific delivery and increase the therapeutic efficacy of the formulation. The mannose-functionalized isoniazid-loaded nanostructured lipid carrier (Man-INH-NLC) formulation was evaluated with respect to various formulation parameters, namely, encapsulation efficiency (EE), drug loading (DL), average particle size (PS), zeta potential (ZP), polydispersity index (PDI), in vitro drug release (DR), and release kinetics. The in vitro inhalation behavior of the developed formulation after nebulization was investigated using an Andersen cascade impactor via the estimation of the mass median aerosolized diameter (MMAD) and geometric aerodynamic diameter (GAD) and subsequently found to be suitable for effective lung delivery. An in vivo pharmacokinetic study was carried out in a guinea pig animal model, and it was demonstrated that Man-INH-NLC has a longer residence time in the lungs with improved pharmacokinetics when compared with unfunctionalized INH-NLC, indicating the enhanced therapeutic efficacy of the Man-INH-NLC formulation. Histopathological analysis led us to determine that the extent of tissue damage was more severe in the case of the pure drug solution of isoniazid compared to the Man-INH-NLC formulation after nebulization. Thus, the nebulization of Man-INH-NLC was found to be safe, forming a sound basis for enhancing the therapeutic efficacy of the drug for improved management in the treatment of pulmonary tuberculosis.

Solid Lipid Nanoparticles Embedded Hydrogels as a Promising Carrier for Retarding Irritation of Leflunomide.

Leflunomide (LEF), a disease-modifying anti-rheumatic drug, has been widely explored for its anti-inflammatory potential in skin disorders such as psoriasis and melanoma. However, its poor stability and skin irritation pose challenges for topical delivery. To surmount these issues, LEF-loaded solid lipid nanoparticles (SLNs) integrated with hydrogels have been developed in the present investigation. SLNs developed by microemulsion techniques were found ellipsoidal with 273.1 nm particle size and -0.15 mV zeta potential. Entrapment and total drug content of LEF-SLNs were obtained as 65.25 ± 0.95% and 93.12 ± 1.72%, respectively. FTIR and XRD validated the successful fabrication of LEF-SLNs. The higher stability of LEF-SLNs (p < 0.001) compared to pure drug solution was observed in photostability studies. Additionally, in vitro anti-inflammatory activity of LEF-SLNs showed good potential in comparison to pure drugs. Further, prepared LEF-SLNs loaded hydrogel showed ideal rheology, texture, occlusion, and spreadability for topical drug delivery. In vitro release from LEF-SLN hydrogel was found to follow the Korsmeyer-Peppas model. To assess the skin safety of fabricated lipidic formulation, irritation potential was performed employing the HET-CAM technique. In conclusion, the findings of this investigation demonstrated that LEF-SLN hydrogel is capable of enhancing the photostability of the entrapped drug while reducing its skin irritation with improved topical delivery characteristics.

Design of mesalamine loaded micro-particles: Preparation, in vitro and in-vivo characterization

The goal of this study was to develop mesalamine (MS) microparticles that could be ingested by the colon without first passing via the stomach and small intestines. Without resorting to the time-consuming and laborious double emulsion solvent diffusion method, microparticles were successfully fabricated using the Box-Behnken Design method. Microparticle production was optimized, and the effects of many parameters were analyzed (X1: Eudragit S100, X2: Span 80 and X3: agitation speed). Using the Box-Behnken design (BBD), we compared the chosen optimized microparticles to the pure drug solution utilizing in vivo pharmacokinetic study for particle size (Y1), entrapment efficiency (Y2), and drug-release (Y3). It was simple to create spherical, free-flowing, smooth-surfaced microparticles with a zeta potential of −36.52 mV and a size distribution of 264.35 ± 6.28–652.34 ± 6.49 nm. Coefficients of 264.35 ± 6.28–652.34 ± 6.49%, 42.31 ± 2.43–89.74 ± 2.17%, and 52.31 ± 0.43–93.51 ± 0.33% from a quadratic model best fit the observed values of dependent variables. Formulation F4 was selected as the best option because it prevented the drug from being released in the upper GIT before it was ready and instead released it only in the colon, where the pH is optimal. The formulation had a particle size of 266.597 μm, an entrapment efficiency of 93.735%, a cumulative drug release of 95.578 percent, and a desirability factor of 0.998. In comparison to drug solution pharmacokinetics, microparticle pharmacokinetics showed a 6.35-fold decrease in Cmax and MS with an appropriately increased half-life of 8.13 h. (13.67 and 3.46). This enhanced bioavailability of MS released from microparticles is probably due to an increase in the half-life, mean residence time (MRT), and area under the concentration–time curve (AUC0-24) of MS. Over a long length of time with no increase in plasma MS level, it became clear that the novel method of MS-loaded microparticles would provide successful therapy for ulcerative colitis. A pharmacodynamic study found that mesalamine-loaded microparticles dramatically decreased colon edema, necrosis, and bleeding compared to free drug solution. Results from this study suggest that mesalamine-loaded microparticles may be an effective pharmaceutical delivery strategy for the management of ulcerative colitis.

DOE supported optimization of biodegradable polymeric nanoparticles based dry powder inhaler for targeted delivery of afatinib in non-small cell lung cancer

Poly (lactic-co-glycolic acid) (PLGA) based nanoparticles are increasingly being used to deliver anticancer agents directly to the lungs. This approach offers targeted delivery of the drug, which minimizes the risk of side effects associated with oral administration. Afatinib-loaded PLGA nanoparticles were fabricated with a double emulsification solvent evaporation method and optimized by a factorial design (32) approach. The optimized batch of afatinib-loaded polymeric nanoparticles exhibited suitable entrapment efficiency (78.15 ± 2.20% w/w), drug loading (3.90 ± 0.11% w/w), particle size (198.1 ± 3.5 nm), and zeta potential (−0.519 ± 0.197 mV). A dry powder-based inhaled drug delivery platform is rapid-acting, handy, and self-administered that is expected to enhance patient compliance. The lyophilization method was used to convert afatinib-loaded PLGA nanoparticles into dry powder form. The formulated afatinib-loaded PLGA nanoparticles dry powder inhaler (PLGA NDPI) demonstrated good flow properties with 77.86 ± 3.02% drug content and 6.883 ± 0.369 μm particle size distribution. With more than 85% of the dosage released from an inhaler device in the eight-stage cascade impactor through an in-vitro lung deposition investigation, the particles also proved their capacity to penetrate the deeper area of the lung. Further, the in-vitro drug release study demonstrated more than 80% drug release from PLGA NDPI at different pH of phosphate buffer solutions. A549 adenocarcinoma cell line cytotoxicity investigation revealed that PLGA NDPI has a stronger potential for suppressing tumour cell proliferation than pure drug solution. Fluorescein isothiocyanate (FITC) encapsulated afatinib PLGA NDPI formulation was more effectively absorbed intracellularly by adenocarcinoma cells than plain FITC dye. Taken together, the results suggest that, the formulated afatinib PLGA NDPI can be a promising approach for targeted lung delivery of the anticancer agent.

Bioanalytical Method Development and Validation for Determination of Rifampicin and Quercetin in Rat Plasma by UHPLC-MS/MS: Applications to Pharmacokinetic Study

UHPLC-MS/MS was utilised to quantitatively analyse Rifampicin and Quercetin-loaded Liquisolid compact in rat plasma. The UPLC Acquity C18 (1.7 μm, 2.1 × 15 mm) column and 0.5 ml/min were used to separate the analyte. In a low-pressure gradient mode, A: In water 0.1 % formic acid and B: In acetonitrile 0.1 % formic acid as the mobile phase. Sample pre-treatment was performed by protein precipitation technique with methanol and acetonitrile (1:1) from rat plasma. As an internal standard (IS), the analyte was found by tracking precursor-to-product ion transformations of 823 → 791.3 m/z for rifampicin, 303 → 257 m/z for quercetin, and 138 → 121 m/z for isoniazid in MRM mode. The proposed technique was validated for precisions (Intraday and Interday) accuracy, linearity, quantification at lower limits, and analyte recovery. The findings showed that the plasma samples inter and intra-day precision and consistency values were determined to be within the acceptable range. After orally administering Liquid solid compact and pure drug solution, which showed a substantial difference in the pace and extent of absorption, the method’s suitability for determining the pharmacokinetic profile of each drug was tested.

Design and Evaluation of Solid Lipid Nanoparticle Eye Drops Containing VRN for Ocular Drug Delivery

As a well-known oral and intravenous antifungal, voriconazole (VRN) has an extensive history of usage in the medical field. Solid lipid nanoparticles (SLNs) have been produced to treat ocular fungal keratitis in the eye. A 32Box-behnken design was used to produce a variety of new formulas for hot-melt extrusion. The SLNs were evaluated by entrapment efficiency (EE percent), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). A series of in-vitro and in-vivo studies were carried out on the new formula. The produced vesicles’ EE, PS, PDI, and ZP values were all good. SLNs eye drops were numerically adjusted to include carbopol, a stabilizer, lipids, and a surfactant, among other substances. ZP of -36.5 ± 0.20 mV, 80.9 ± 1.02 % EE, 205 ± 9.1 nm PS, and 0.015 PDI were all included in the data. For example, by differential scanning calorimetry (DSC) and fourier-transform infrared (FTIR), it was discovered that the crystallinity of the drug had been reduced. The in-vitro release study and the SLNs and carbopol-based eye drops prepared with ultrasonication method demonstrated sustained release up to 48 hours. Comparing VRN-SLNs pharmacokinetics to that of pure drug solution, researchers discovered an area under the curve (AUC) and Cmax three times higher and a factor of five times higher, respectively (both P 0.01). By functioning as a carrier, SLNs may increase the bioavailability of VRN in the eye. The in-vivo studies were performed by infecting the rats with candida species. It was observed that VRN-loaded SLNs eye drops were more efficient in treating candidiasis. Results indicate that VRN-loaded SLNs eye drops provide a sustaining VRN topical effect and quick relief from fungal infection.

The Study of Spray-Freeze-Drying Technique for Development of Novel Combination pMDIs, Part II: In Vitro and In Vivo Evaluations

AbstractThe mometasone furoate (MF) and formoterol fumarate dihydrate (FF) inhalable microparticles prepared by different methods, such as micronized active pharmaceutical ingredients (APIs), microparticles of APIs prepared by spray-freeze drying technique (SFD APIs), and phospholipid microparticles of APIs prepared by SFD (SFD Lip-APIs), showed different inhaled drug delivery characteristics. Study on the physicochemical characteristics of those microparticles and the effect of matrix excipients on pharmacokinetic (PK) behaviors of inhalable microparticles is helpful for the development of new methods for inhalable microparticles with excellent performance of inhalation characteristics. In this study, the crystal state of the microparticles was investigated by powder X-ray diffraction and differential scanning calorimetry. The density was investigated by a bulk density method. The suspension and dispersion characteristics were determined by observing its state in hydrofluoroalkane (HFA). Meanwhile, the PK behaviors of SFD Lip-APIs in beagle dogs were also investigated by airway administration to evaluate the effect of phospholipids on drug release. The results indicated that the presence of phospholipids prevents the formation of solid bridges bonding to each other during SFD of pure drug solutions. In comparison to the conventional micronized microparticles, inhalable drug–phospholipid microparticles were easily dispersed and suspended in HFA. The embedded drugs were in a crystal state that endowed a better physical stability, and most interestingly, have similar PK behavior to the control (a mixed solution of MF/FF), suggesting that the phospholipids, as matrix excipients, had no effect on absorption. Given above, our designed SFD phospholipid microparticles may represent an efficient carrier for pulmonary delivery of MF and FF for further clinical treatment.

Designing Deferoxamine-Loaded Flaxseed Gum and Carrageenan-Based Controlled Release Biocomposite Hydrogel Films for Wound Healing.

In this study, biocomposite hydrogel films made from flaxseed gum (FSG)/kappa carrageenan (CGN) were fabricated, using potassium chloride as a crosslinker and glycerol as a plasticizer. The composite films were loaded with deferoxamine (DFX), an iron chelator that promotes neovascularization and angiogenesis for the healing of wounds. The properties of the biocomposite hydrogel films, including swelling, solubility, water vapor transmission rate, tensile strength, elongation at break, and Young’s modulus studies, were tested. The films were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). In addition, drug release studies in PBS at pH 7.2 were investigated. In vivo analysis was performed by assessing the wound contraction in a full-thickness excisional wound rat model. Hematoxylin & eosin (H & E) and Masson’s trichome staining were performed to evaluate the effect of the films on wound healing progress. The visual and micro-morphological analysis revealed the homogenous structure of the films; however, the elongation at break property decreased within the crosslinked film but increased for the drug-loaded film. The FTIR analysis confirmed the crosslinking due to potassium chloride. A superior resistance towards thermal degradation was confirmed by TGA for the crosslinked and drug-loaded films. Drug release from the optimum film was sustained for up to 24 h. In vivo testing demonstrated 100% wound contraction for the drug-loaded film group compared to 72% for the pure drug solution group. In light of the obtained results, the higher potential of the optimized biocomposite hydrogel film for wound healing applications was corroborated.

Exploring ex vivo peptideolysis of thymopentin and lipid-based nanocarriers towards oral formulations

The oral delivery of medicines is the most popular route of administration for patients. However, thymopentin (TP5) is only available in the market in forms for parenteral administration. In large part, this is because of extensive peptidolytic degradation in the gastrointestinal tract (GIT), which decreases the amount of TP5 available for absorption. This study aims to understand the extent of TP5 peptideolysis and determine effective inhibitors and suitable lipid-based nanocarriers to aid in the development of an effective oral delivery formulation. Enzymatic degradation kinetics of TP5 was investigated in the presence or absence of mucosal and luminal components extracted from various parts of the rat intestine, including the duodenum, jejunum, ileum, and colon. Inhibition of TP5 enzymatic peptidolysis was screened in the presence or absence of EDTA, trypsin and chymotrypsin inhibitors from soybean (SBTCI), and bestatin. TP5 with SBTCI was loaded into lipid-based nanocarriers, including microemulsions, niosomes and solid lipid nanoparticles. These TP5-loaded nanocarriers were investigated through characterization of morphology, particle size, zeta potential, entrapment efficacy (EE%), and ex vivo rat intestinal degradation studies to select a lead formulation for a future oral drug delivery study. The degradation kinetics of TP5 followed pseudo-first-order kinetics, and the biological metabolism of TP5 was displayed in the presence of luminal contents, indicating that TP5 is sensitive to luminal enzymes. Notably, a considerable decrease in TP5 peptidolysis was found in the presence of SBTCI, bestatin, and EDTA. TP5 and SBTCI were loaded into three lipid-based delivery systems, displaying superior protection under ex vivo intestinal luminal contents and mucosal homogenates for 6 h compared with the pure drug solution. These findings suggest that using select inhibitors and lipid-based nanocarriers can decrease peptide degradation and may improve oral bioavailability of TP5 following oral administration.

An Investigation for Skin Tissue Regeneration Enhancement/Augmentation by Curcumin-Loaded Self-Emulsifying Drug Delivery System (SEDDS).

Diabetes, one of the global metabolic disorders, is often associated with delayed wound healing due to the elevated level of free radicals at the wound site, which hampers skin regeneration. This study aimed at developing a curcumin-loaded self-emulsifying drug delivery system (SEDDS) for diabetic wound healing and skin tissue regeneration. For this purpose, various curcumin-loaded SEDDS formulations were prepared and optimized. Then, the SEDDS formulations were characterized by the emulsion droplet size, surface charge, drug content/entrapment efficiency, drug release, and stability. In vitro, the formulations were assessed for the cellular uptake, cytotoxicity, cell migration, and inhibition of the intracellular ROS production in the NIH3T3 fibroblasts. In vivo, the formulations’ wound healing and skin regeneration potential were evaluated on the induced diabetic rats. The results indicated that, after being dispersed in the aqueous medium, the optimized SEDDS formulation was readily emulsified and formed a homogenous dispersion with a droplet size of 37.29 ± 3.47 nm, surface charge of −20.75 ± 0.07 mV, and PDI value of less than 0.3. The drug content in the optimized formulation was found to be 70.51% ± 2.31%, with an encapsulation efficiency of 87.36% ± 0.61%. The SEDDS showed a delayed drug release pattern compared to the pure drug solution, and the drug release rate followed the Fickian diffusion kinetically. In the cell culture, the formulations showed lower cytotoxicity, higher cellular uptake, and increased ROS production inhibition, and promoted the cell migration in the scratch assay compared to the pure drug. The in vivo data indicated that the curcumin-loaded SEDDS-treated diabetic rats had significantly faster-wound healing and re-epithelialization compared with the untreated and pure drug-treated groups. Our findings in this work suggest that the curcumin-loaded SEDDS might have great potential in facilitating diabetic wound healing and skin tissue regeneration.

Development and Evaluation of Self Micro Emulsifying Drug Delivery System (SMEDDS) for Nebivolol Hydrochloride

The present investigation aimed to prepare a self micro emulsifying drug delivery system (SMEDDS) for the dissolution enhancement of nebivolol hydrochloride. The main objective of this work was to develop, characterize, and evaluate a solid SMEDDS prepared by using the adsorption technique of a liquid SMEDDS to improve the solubility and dissolution rate of nebivolol hydrochloride. The excipients were chosen based on the high solubility of nebivolol hydrochloride, and their concentrations were optimized by constructing ternary phase diagrams. Thirty-two combinations were prepared using oil (Labrafac Lipophile WL 1349), surfactant (Kolliphor RH 40), and co-surfactant (Gelucire 44/14). Self-emulsification time, dilution studies, and thermodynamic stability studies were satisfactory. The in vitro nebivolol release profile showed a faster rate of dissolution compared with the pure nebivolol hydrochloride suspension and marketed formulation. The droplet size was in the range of 132.8±22.1 to 955.7±15.5 nm and zeta potential in the range -7.2±0.53 mV to -46.4±0.32 mV for the selected formulations. Formulation N17 (Labrafac Lipophile WL 1349 -10%w/w, Kolliphor RH40-72%w/w, Gelucire 44/14- 18%w/w) was considered as optimized formulation and showed drug release of 97.26 ± 1.16% in 0.1 N HCl in 120 minutes, the particle size of 132.8±22.1 nm and zeta potential of -46.4±0.32 mV. Thus, the present studies ratify that the bioavailability was improved by nebivolol SMEDDS formulation. The optimized liquid SMEDDS was further used for the preparation of Solid SMEDDS (S-SMEDDS) formulations by using adsorption carriers. The optimized Solid SMEDDS formulation exhibited 95.38 ± 0.76% in vitro drug releases, which was significantly higher than that of the drug solution. The optimized formulation of nebivolol-loaded S-SMEDDS exhibited complete in vitro drug release in 120 min as a compared pure drug solution. The present result confirmed the potential use of SMEDDS to improve the dissolution and oral bioavailability of poorly water-soluble nebivolol.&#x0D;

β-Artemether and Lumefantrine Dual Drug Loaded Lipid Nanoparticles: Physicochemical Characterization, Pharmacokinetic Evaluation and Biodistribution Study.

β-artemether (BAT) and lumefantrine (LFT) combination therapies are well recognized for the treatment of malaria. However, the current conventional formulations have several drawbacks. The study aims to develop novel lipid nanoparticles (LNP) for efficient delivery of BAT and LFT. The LNP were prepared by solvent injection method and optimized by the Box-Behnken experimental design to achieve the desired particle size, maximum entrapment efficiency (EE), and percentage drug release. BAT and LFT in rat plasma were estimated by liquid chromatographytandem mass spectrometry (LC-MS/MS). Freeze-dried LNP comprised of 78.74% (w/w) lipid, 15.74% (w/w) surfactant, 3.93% (w/w) co-surfactant and 1.57% mannitol with respect to the total inactive components. Mean particle size and zeta potential were found to be 140.22 ± 1.36 nm and -35.23 mv, respectively. EE was 80.60 ± 3.85% for BAT and 69.64 ± 2.63% for LFT. The optimized formulation exhibited a biphasic release profile in phosphate buffer (pH 7.2). In vivo study revealed an increased bioavailability of BAT and LFT from dual drug loaded LNP compared to the pure drug solution. Moreover, the tissue distribution study confirmed the high uptake of both the drugs in the liver and spleen. The study demonstrated the potential use of the developed formulation for oral administration in the treatment of malaria.

Formulation Development and Evaluation of Pravastatin-Loaded Nanogel for Hyperlipidemia Management.

Hyperlipidemia is a crucial risk factor for the initiation and progression of atherosclerosis, ultimately leading to cardiovascular disease. The nanogel-based nanoplatform has emerged as an extremely promising drug delivery technology. Pravastatin Sodium (PS) is a cholesterol-lowering drug used to treat hyperlipidemia. This study aimed to fabricate Pravastatin-loaded nanogel for evaluation of its effect in hyperlipidemia treatment. Pravastatin-loaded chitosan nanoparticles (PS-CS-NPs) were prepared by the ionic gelation method; then, these prepared NPs were converted to nanogel by adding a specified amount of 5% poloxamer solution. Various parameters, including drug entrapment efficacy, in vitro drug release, and hemolytic activity of the developed and optimized formulation, were evaluated. The in vitro drug release of the nanogel formulation revealed the sustained release (59.63% in 24 h) of the drug. The drug excipients compatibility studies revealed no interaction between the drug and the screened excipients. Higher drug entrapment efficacy was observed. The hemolytic activity showed lesser toxicity in nanoformulation than the pure drug solution. These findings support the prospective use of orally administered pravastatin-loaded nanogel as an effective and safe nano delivery system in hyperlipidemia treatment.

Development and Validation of UV Spectrophotometric Method for Determination of Tacrolimus in Bulk and Capsule Dosage Form

Background The present study aimed to develop and validate a rapid robust effective specific and accurate UV-Vis method for the determination of Tacrolimus in pharmaceutical dosage forms according to International Conference on Harmonization ICH Q2 R1 guidelines.Methodology The method development was done using phosphate buffer of pH 6.8. The method validation parameters like linearity precision accuracy robustness and ruggedness were assessed for the developed method. Pure drug solutions were prepared using Phosphate buffer pH 6.8 the aliquots of concentration range 1-10 microgmL and therefore the linear regression coefficient R2 was 0.999.Results The optimum lambdamax was at 295 nm. The developed method was precise within the interday and intraday studies and showed percentage RSD of 1.731 and 1.243 respectively. Thus a precise simple and cost-effective UV-Vis method for the determination of Tacrolimus was developed.Conclusion The method developed was found to be precise robust simple and cost-effective for the determination of Tacrolimus in bulk and in pharmaceutical dosage forms with regression coefficient R2 of 0.999.

Quercetin and piperine enriched nanostructured lipid carriers (NLCs) to improve apoptosis in oral squamous cellular carcinoma (FaDu cells) with improved biodistribution profile

Oral squamous cellular carcinoma (OSCC) is considered a life-threatening disease with detection in late stages, which forces us to opt for dangerous treatment with a combination of chemotherapy and radiotherapy. Herbal components such as piperine and quercetin are derived from edible sources, proving their anticancer potential against oral cancer cells in vitro. Encapsulation into lipid matrix-mediated nanostructured lipid carriers (NLCs) can make both drugs bio-accessible. NLCs were synthesised using the high shear homogenisation method and characterised for their physicochemical properties, followed by in vitro cellular evaluation in FaDu oral cancer cells. NLCs showed negatively charged particles smaller than 180 nm with a polydispersity index (PDI) of <0.3. Both drugs were found to encapsulate sufficiently, with >85% entrapment efficiency and an improved drug release profile compared to their pristine counterparts. Differential scanning calorimetry (DSC) thermograms showed conversion into an amorphous matrix in lyophilized NLCs, which was supported by X-ray diffraction (XRD) analysis. The cytotoxicity assay showed the IC50 concentration for dual drug-loaded NLCs, which was more effective than the pure drug solution. NLCs were found to be internalised in cells in a short time with an almost 95% co-localization rate. Dual drug-loaded NLCs showed maximum depolarisation of the mitochondrial membrane along with more apoptotic changes. Improved apoptosis was confirmed in NLCs using flow cytometry. The in vivo biodistribution of Coumarin-6 labelled NLCs in rats confirmed their efficient distribution in various parts of the oral cavity through oral administration. Optimised dual drug-loaded NLCs provide a better option for delivering both drugs through a single lipid matrix against oral cancer.