Impact of hydrolyzed gelatin and hydroxypropyl-β-cyclodextrin as polymeric excipients on physical stability and injectability of high-concentration protein suspensions.

Analysis of molecular weight of mixed poly (lactide-co-glycolide) in Risperidone microspheres based on separation method.

Poly(lactide-co-glycolide) polymers (PLGAs) are indispensable biodegradable matrices for long-acting parenteral (injectable) microsphere formulations. To modulate drug release kinetics and mitigate burst release in these complex injectable systems, PLGAs with varying lactide:glycolide (L:G) ratios are often employed in combination. While essential for ensuring batch-to-batch consistency and developing generic long-acting injectables, characterizing the individual properties of mixed PLGAs remains technically challenging. This study establishes a simple and accurate method to separate and characterize PLGA 7525 5A and PLGA 5050 2.5A within risperidone microspheres based on their solubility differences (semi-solvent principle). Trichloroethylene was identified as the optimal separation solvent, with n-propyl acetate serving as the washing solvent. The method was optimized by investigating parameters such as solvent volume, temperature, and mechanical assistance, with the addition of glass beads proving critical for effective separation. Molecular weight (Mw) analysis was performed using Gel Permeation Chromatography (GPC) on Agilent PLgel columns (connected in series) with tetrahydrofuran (THF) as the mobile phase. The method demonstrated excellent linearity (R2 = 0.9998) within the calibration range of 1220-554,000 g·mol⁻¹ (Polystyrene equivalent). Precision was high, with RSD values of 0.33% (n=6) for the supernatant Mw and 2.1% (n=6) for the sediment Mw. The method's discriminatory ability was validated using simulated single-polymer degradation and mixed degraded microspheres. In conclusion, this method enables independent quality control of individual PLGA components within complex injectable matrices, providing a vital analytical tool for the key characteristic evaluation and bioequivalence assessment of complex generic parenteral formulations.

Sustained-Release Polymeric Submicron Microspheres of Valsartan: Formulation, Characterization, and Release Kinetics

Physicochemical and Stability Study of Chitosan-Coated Nanoliposomes: Effects of Polymer Molecular Weight and Ultrahigh Pressure Homogenization-UHPH

This study evaluated the effect of chitosan with a high degree of deacetylation (75–85%) and three different molecular weights—low (50–190 kDa), medium (190–310 kDa), and high (310–375 kDa)—on the coating of vesicular systems. Chitosan solutions were characterized in acidulated aqueous medium by determining changes in pH, electrical conductivity, zeta potential, surface tension, viscosity, transmittance, particle size, and polydispersity index (PDI) with respect to polymer concentration. Subsequently, nanoliposomes were developed using an ethanol injection method assisted by ultra-high-pressure homogenization (UHPH) prior to coating. The characterization of the vesicular systems involved particle size analysis, polydispersity index (PDI), and zeta potential, which were evaluated at zero time and at the fourth week prior to storage at 4 °C and 40 °C. The physicochemical characterization of chitosan solutions displayed an inflection point at 1 × 10−3 M, which was taken as the coating concentration. In general, non-coated liposomes ranged between 150 and 200 nm, with low polydispersity (<0.3) and negative zeta potentials around ~−43 mV. Chitosan coating significantly increased particle size and PDI, while decreasing zeta potential values, but within the same negative value range, suggesting a slight interfacial coating effect. Finally, the systems subjected to UHPH and coated with high- and medium-molecular-weight chitosan showed interesting stabilization against storage conditions in the thermal stress tests.

Phytotherapeutics self-microemulsifying systems in pellet dosage form for enhanced intestinal drug delivery: formulation, stability, and in-vivo performance

Abstract Self-microemulsifying drug delivery systems (SMEDDS) containing volatile phytotherapeutics such as thymol (T), carvacrol (C), and eugenol (E) present significant formulation challenges, even when solidified. Their instability and interactions with coatings often hinder intestinal delivery. To address these limitations, we developed solid SMEDDS consisting of pellets (microcrystalline cellulose/magnesium aluminometasilicate/chitosan) and enteric capsules (CEC) for enhanced intestinal delivery. Based on solubility and pseudo-ternary phase diagrams, SMEDDS formulations (SES1-3) differing in component ratios (glycerol monooleate/caprylocaproyl macrogol-8 glycerides/diethylene glycol monoethyl ether) with 5% w/w of each drug were identified, demonstrating nano-scale droplet sizes (PDI <0.4) and showing no phase separation over 6 months. Thermodynamic stability and liquid-state NMR revealed particle size variations with preserved structural integrity. The lead formulation SES1 exhibited superior ex-vivo intestinal permeation (T-SES1). CECs filled with T-, C-, and E-loaded SES1 pellets, respectively, prepared via extrusion/spheronization, exhibited in-vitro gastro-resistant release, and achieved > 85% drug release within 120  min after a pH change to 6.8 during a one-year stability study (25 °C; 60% RH). FTIR-ATR analysis of the CEC internal surface confirmed the temperature-dependent restructuring of hypromellose and E sorption, a phenomenon not observed with C or T, which is likely attributable to physicochemical distinctions. Oral administration of CEC with T-SES1-pellets (0.5  mg/kg) in piglets demonstrated a delayed peak plasma concentration (Cmax 11.67  ng/mL at 9 h) and sustained systemic exposure (AUC 119.8 ng·h/mL). These in-vivo findings substantiate the gastro-protective effect and enhanced intestinal absorption, positioning the pellet/CEC system as a promising strategy for the application of volatile phytotherapeutics in current pharmacotherapy.

Lutein-loaded Pickering high internal phase emulsions stabilized by protein-polyphenol-polysaccharide self-assembled particles: Interfacial behavior, in vitro/in vivo stability and release.

In vitro tests indicated that HIPEs enhanced lutein's resistance to storage, heat, and UV exposure while facilitating sustained intestinal release, resulting in a lutein bioaccessibility of 43.73 ± 1.44%.

Soy Protein Isolate-β-Cyclodextrin Microencapsulation Boosts Stability and Intestinal Delivery of α-Linolenic Acid-Rich Structured Lipids: Oxidation, Digestion, and Molecular Docking Evaluation.

In vitro simulated digestion demonstrated its characteristic intestinal sustained-release behavior, which provides preliminary in vitro evidence that may favor enhanced intestinal absorption of α-linolenic acid (ALA); however, further cellular or animal trials are required to quantitatively validate its actual in vivo bioavailability improvement.