Design and Optimization of Transethosomal Drug Delivery Systems for Ritonavir: Comparative Evaluation, Characterization, and Release Kinetics

BOX–BEHNKEN DESIGN APPROACH FOR OPTIMIZATION OF ACECLOFENC LOADED TRANSFEROSOMAL GEL FOR ENHANCED TRANSDERMAL DELIVERY

Objective: The current study aimed to develop and optimize an aceclofenac (ACF)-loaded transferosomal gel for transdermal drug delivery using a Box–Behnken design (BBD), thereby enhancing bioavailability and reducing systemic side effects. Methods: Using different ratios of Span 80 and phosphatidylcholine (PDC), transferosomes were developed using the rotary thin-film hydration method and optimized with BBD. The independent variables in transferosome preparation were the amount of Span 80 and PDC. The dependent variables were entrapment efficiency (EE), drug release (DR), and drug content (DC). Drug and excipient compatibility were determined using differential scanning calorimetry and Fourier transform infrared spectroscopy. The prepared transferosomes were characterized for DC, particle size distribution, EE, zeta potential, polydispersity index (PDI), in vitro DR and morphology by scanning electron microscopy (SEM). The optimized ACF transferosomal formulation was incorporated into a gel and evaluated for pH, spreadability, viscosity, ex vivo skin permeation, and stability. Results: The optimized formulation had a spherical shape, a vesicular size of 157±27.16 nm, a PDI of 0.26±0.058, and an EE of 89.69±4.2%. The optimized transferosomal gel showed an ex vivo permeation of 3900±57.21 μg/cm2 over 24 h through the skin of albino Wistar rats. SEM demonstrated the smooth surface. The DR kinetics adhered to a zero-order model, showing a sustained release pattern and confirming improved transdermal penetration of ACF through transferosome technology. Conclusion: Transferosomes are effective nanoscale carriers for ACF, significantly enhancing the transdermal penetration of ACF through transferosome technology as confirmed by ex vivo skin permeation studies.

Development and Characterization of Solid Dispersions of Azithromycin Using Poloxamer 407 and Syloid 244FP®

Solid self-microemulsifying drug delivery systems in modern pharmaceutics: design, characterization, and clinical applications

Background: Approximately 40% of marketed medicines and 70% of pipeline products exhibit poor aqueous solubility, leading to inconsistent oral bioavailability and impaired efficacy. S-SMEDDS represent a revolutionary approach for converting liquids into stable solid dosage forms. Methodology: Methods employed to prepare S-SMEDDs include adsorption onto carriers, spray drying, hot-melt extrusion, and freeze-drying. Characterization includes assessing self-emulsifying behavior, dynamic light scattering, powder diffraction, and thermal analysis. Results and Discussion: Depending on the drug's characteristics, the formulation composition, and the study conditions, S-SMEDDS can increase bioavailability by two to ten times. However, for some extremely lipophilic BCS Class II and IV pharmaceuticals, significantly greater benefits (up to ~50-fold) have been documented. Several investigations have demonstrated that S-SMEDDS exhibit better physical and chemical stability than liquid systems under ICH Q1A(R2) accelerated storage conditions due to reduced lipid mobility and a lower risk of phase separation. Applications extend to the treatment of cardiovascular, oncological, and endocrine disorders with improved pharmacodynamic efficacy. The multiple absorption mechanisms in S-SMEDDS include improved solubilization, reduced precipitation, lymphotropic delivery, and inhibition of efflux pumps. They demonstrate higher chemical and physical stability, precise dosing, and better patient adherence when compared to traditional liquid counterparts. Conclusion: S-SMEDDS constitute an established pharmaceutical platform that overcomes the drawbacks associated with liquid lipid drug delivery systems. Their high effectiveness, manufacturability, and compatibility with novel technologies such as three-dimensional printing and artificial intelligence position them to be the foundation for precision oral drug delivery.

Formulation, evaluation and characterization of fexofenadine IR and paracetamol SR multiparticulate drug delivery system

Abstract: Background: Multiparticulate Drug Delivery (MDD) system are particularly considered as well suited systems for controlling oral preparations that have low risk of dose-dumping. Objectives: The current research work was aimed to prepare Fexofenadine HCl immediate release (IR) and Paracetamol sustained release (SR) pellets in a single dosage unit for the treatment of Allergic Rhinitis. Extrusion-spheronization was used to fabricate pellets. Methods: The formulations were analyzed for several parameters, including micromeritic studies, Friability, Weight variation test, Swelling, X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), in-vitro release and stability studies. Results: The results showed that the formulated pellets have an excellent flowability (23.01° to 25.23°), bulk density falls in the range of 1.23 g cm-3 to 1.42 g cm-3, tapped density ranges 1.43 g/cm3 1.58 g/cm3, carr’s compressibility index lie between 10.31 % to 15.17 %, Hausner's ratio ranges 1.11 to 1.18 which concluded pellets had good flow properties. Friability was less than 1%; the T6 formulation showed the maximum swelling of 99.28%. No interaction between excipient and drug was found. T6 showed a drug release of 99.08% in 24 hours. Conclusion: The research effectively demonstrated that preparing a single-unit dosage form of paracetamol and fexofenadine is a safe, simple and promising technique for SR of Paracetamol, thereby increasing patient compliance by reducing the dosage frequency.

FORMULATION, OPTIMIZATION AND EVALUATION OF KETOPROFEN-LOADED EUDRAGIT MICROSPONGES INCORPORATED INTO TABLET DOSAGE FORM

The present study focused on the formulation, optimization, and evaluation of Ketoprofen-loaded microsponges intended for sustained drug delivery using the quasi-emulsion solvent diffusion method. Ketoprofen, a widely prescribed non-steroidal anti-inflammatory drug (NSAID), is commonly used for the management of pain and inflammatory disorders. However, its short biological half-life and the need for repeated dosing may result in gastrointestinal side effects and reduced patient adherence. To address these limitations, sustained release microsponge tablets were developed using Eudragit RS100 as the rate-controlling polymer and Polyvinyl Alcohol (PVA) as the stabilizing agent. Preformulation studies such as organoleptic evaluation, melting point determination, UV-visible spectroscopy, and FTIR analysis were carried out to confirm the purity and compatibility of the drug with selected excipients. Ketoprofen showed a maximum absorption wavelength at 260 nm and demonstrated good linearity within the concentration range of 2–16 µg/mL. FTIR spectra indicated the absence of any significant interaction between the drug and excipients. The prepared microsponges were characterized for particle size, morphology, production yield, entrapment efficiency, and in-vitro drug release behavior. SEM studies confirmed the formation of spherical, porous, and discrete microsponges with particle size ranging between 9.28 µm and 23.42 µm. Among all formulations, batch F3 exhibited the highest production yield (89.00 ± 0.15%) and maximum loading efficiency (88.60 ± 0.08%). DSC and XRD investigations suggested partial conversion of crystalline Ketoprofen into an amorphous form within the polymeric matrix without any major drug–polymer incompatibility. The optimized microsponge formulation was compressed into tablets and further evaluated for pre-compression and post-compression characteristics. Formulation F3 demonstrated acceptable hardness, low friability, satisfactory drug content, and prolonged drug release of 98.60% over a period of 12 hours. Drug release kinetic studies revealed that the optimized formulation followed Higuchi and Korsmeyer–Peppas release models, indicating diffusion-mediated anomalous drug release. Accelerated stability studies conducted according to ICH guidelines confirmed that the optimized formulation remained stable for three months under prescribed storage conditions. The findings of the study suggest that microsponge technology offers an effective approach for sustained delivery of Ketoprofen by improving drug entrapment, controlling release behavior, enhancing formulation stability, and increasing patient compliance.

Formulation, Characterization, and Preliminary In Vitro Evaluation of Letrozole Incorporated Eudragit® RS 100 Nanoparticles Using HepG2 Cells.

INTRODUCTION/OBJECTIVE Letrozole (LTZ)-loaded polymeric nanoparticles (PNPs) were formulated with Eudragit® RS100 to investigate their potential as a preliminary drug delivery system for hepatocellular carcinoma (HCC). METHODS Nanoparticles were prepared using the spray-drying technique with a Büchi B-90 Nano Spray Dryer and characterized in terms of morphology, particle size, polydispersity index (PDI), zeta potential, drug loading efficiency, thermal and structural characteristics, in vitro release behavior, and preliminary cytotoxicity. RESULTS SEM analysis demonstrated the formation of predominantly spherical particles with relatively smooth surfaces. The prepared nanoparticles exhibited initial particle sizes ranging between 253 nm and 425 nm, with PDI values of 0.3-0.4 and positive zeta potential values between 36 and 48 mV. Encapsulation efficiency (EE%) and drug loading (DL%) values were determined as 47.9%-56.9% and 9.1%-18.6%, respectively. Thermal and structural analyses indicated the molecular dispersion of LTZ within the polymeric matrix. In vitro release studies conducted at pH 7.4 demonstrated an initial burst release, followed by a sustained drug release profile over 24 h, with cumulative drug release reaching almost 80%. The preliminary cytotoxicity of the formulations was evaluated using the methylthiazolyl-diphenyl-tetrazolium bromide (MTT) assay on human hepatocellular carcinoma (HepG2) and healthy human dermal fibroblast (BJ) cell lines. Free LTZ demonstrated an IC50 value of 142.76 µg/mL against HepG2 cells, whereas the optimized nanoparticle formulation exhibited an IC50 value higher than 121.85 µg/mL. DISCUSSION The obtained results confirmed the successful development of LTZ-loaded polymeric nanoparticles with suitable physicochemical properties, efficient drug encapsulation, and sustained release behavior. The positive surface charge and nanoscale size may support formulation stability. Furthermore, the nanoparticles preserved the cytotoxic activity of LTZ, indicating their potential as an effective drug delivery system. CONCLUSION Overall, the findings suggest that the developed nanoparticles constitute a promising drug delivery system for further investigation in HCC-related therapy. However, additional mechanistic studies and in vivo evaluations are required to comprehensively assess their true therapeutic potential.