Formulation and characterization of tramadol-loaded IPN microgels of alginate and gelatin: Optimization using response surface methodology

Abstract

Tramadol-loaded interpenetrating polymer network (IPN) alginate-gelatin (AG) microgels (MG) were prepared by the chemical cross-linking technique with glutaraldehyde as cross-linking agent and were optimized using response surfaces. A central composite design for 2 factors, at 3 levels each, was employed to evaluate the effect of critical formulation variables, namely the amount of gelatin (X 1 ) and glutaraldehyde (X 2 ), on geometric mean diameter, encapsulation efficiency, diffusion coefficient (D), amount of mucin adsorbed per unit mass (Q e ) and 50 % drug release time (t 50 ). Microgels with average particle size in the range of 44.31-102.41 mm were obtained. Drug encapsulation up to 86.5 % was achieved. MGs were characterized by FT-IR spectroscopy to assess formation of the IPN structure and differential scanning calorimetry (DSC) was performed to understand the nature of drug dispersion after encapsulation into IPN microgels. Both equilibrium and dynamic swelling studies were performed in pH 7.4 phosphate buffer. Diffusion coefficients and exponents for water transport were determined using an empirical equation. The mucoadhesive properties of MGs were evaluated in aqueous solution by measuring the mucin adsorbed on MGs. Adsorption isotherms were constructed and fitted with Freundlich and Langmuir equations. In vitro release studies indicated the dependence of drug release on the extent of cross-linking and the amount of gelatin used in preparing IPNs. The release rates were fitted to a power law equation and Higuchi's model to compute the various drug transport parameters, n value ranged from 0.4055 to 0.5754, suggesting that release may vary from Fickian to quasi-Fickian depending upon variation in the formulation composition.

Biodegradable Gelatin Microspheres as Controlled Release Intraarticular Delivery System: The Effect of Formulation Variables

“…This result can be rationalized that the presence of more gelatin and thus higher viscosity of internal phase, causes formation of larger droplets in continuous phase and increase microspheres size. Also, as was reported by previous studies, at constant amount of gelatin, employing higher GA concentration led to reduction of size of microspheres, which could be attributed to the formation of more rigid network structure in the presence of higher cross-linking agent and in turn more shrinkage of prepared microspheres [25,26] . On the other hand, according to Saravanan et al, drug loading enhancement could increase average size of microparticles [20] .…”

“…In addition, dissolution of drug from microspheres with more EE values could facilitate drug diffusion through interconnected channels [29,30] . Based on the previous studies, concentration of both gelatin and GA solution has significant effect on release profile of microspheres [25,26] . In fact the ratio of crosslinking agent to polymer can change drug release profile.…”

“…Also increasing GA concentration had a positive effect on the EE values. Probably, due to the high concentration of GA solution, a rigid network was formed that restricts leaching of the drug molecules during preparation procedure [25] .…”

Eudragit S-100 coated sodium alginate microspheres of naproxen sodium: Formulation, optimization and in vitro evaluation / Alginatne mikrosfere naproksen natrija obložene Eudragitom S-100: Priprava, optimizacija i in vitro vrednovanje

“…This result may be due to the increase in sodium alginate concentration leading to the formation of relatively strong walls of microspheres, and thereby retardation of drug release. Further, the increase in polymer chain entanglement and subsequent low dissolution of the polymer might be responsible for the retardation of drug release from the microspheres (19). Core microsphere formulation NM5 showed maximal drug release at pH 7.4 (98.42 %) compared to other core microsphere formulations.…”

Design of an Interpolyelectrolyte Gastroretentive Matrix for the Site-Specific Zero-Order Delivery of Levodopa in Parkinson’s Disease

“…The experimental mucoadhesion studies can be correlated to these in silico findings as we propose that PLLN may swell readily in contact with hydrated mucous membranes and become progressively rubbery due to uncoiling of polymer chains which may further result in increased mobility of the polymer chains producing a large adhesive surface for maximum contact with the mucosa and flexibility for interpenetration with the mucosa (32). In addition, a few of the characteristics that are responsible for increased hydrogel mucoadhesive properties include (1) high quantity of Hbonding chemical groups (hydroxyls and carboxyls), (2) anionic surface charges, (3) high polymer molecular mass, (4) high polymer chain flexibility, and (5) surface tensions that will induce spreading into the mucus layer (33).…”