Development of reconstitutable suspensions containing diclofenac sodium-loaded microspheres for pediatric delivery

Abstract

Effective clinical utilisation of non-steroidal anti-inflammatory drugs, such as diclofenac sodium (DS) is significantly limited by their ulcerogenic potential and poor bioavailability after oral administration. The objective of this work was to develop reconstitutable pediatric suspensions of DS-loaded microspheres prepared with an acrylic polymer (Eudragit RS) for improved pediatric delivery of DS. The microspheres were prepared by the water-in-oil-in-water or solid-in-oil-in-water emulsion techniques. Enviromental scanning electron microscopy observations clearly showed that microspheres have spherical shape. The drug entrapment efficiency of these microspheres was found 47.96 ± 0.79% to 88.57 ± 0.59% and their average particle sizes were 23.94-60.78 µm, which are within the desired range for the development of suspension formulation. The in vitro dissolution indicated prolonged sustained release of DS over 8 h. The results of preliminary characterisation studies of suspensions show that a liquid pharmaceutical preparation for oral administration capable of providing a sustained release of DS was successfully obtained.

Solid-in-Oil-in-Water Emulsion: An Innovative Paradigm to Improve Drug Stability and Biological Activity

“…FTIR peaks of microspheres were almost unchanged suggesting no bond formation or chemical interaction between drug and polymer. This suggests that s-o-w emulsion system is advantageous for entrapment of diclofenac [ 50 ].…”

“… Further studies need to be done to analyze the integrity of delicate materials encapsulated within the matrix of microspheres [ 121 ]. As there are limited studies related to s-o-w emulsion, detailed investigation needs to be done to determine the correct weight of therapeutic agent and volume of oil, its ratio, type of polymer/copolymer, and/or surfactant along with its concentration so as to develop a compatible formulation with optimal properties [ 32 , 38 , 44 , 50 , 55 ]. …”

Amfoteri̇si̇n-B Enkapsüle Edi̇lmi̇ş Nanoparti̇külleri̇n Anti̇mi̇krobi̇yal Potensi̇ni̇n Değerlendi̇ri̇lmesi̇ İçi̇n Farmakope Yöntemi̇ni̇n Uygulanmasi

“…They can increase the loading capacity and stability of drugs, reduce their toxicity and side effects, prolong their circulation time and half-life, and improve their pharmacokinetics and pharmacodynamics. Polymeric micro and nanoparticles for drug molecules encapsulation have been used for delivering various types of drugs, such as anticancer agents [4], anti-inflammatory agents [5], antibiotics, antiviral agents, vaccines, gene therapy vectors, and imaging contrast agents [6]. Polymeric nanoparticles for drug molecule encapsulation have shown promising results in preclinical and clinical studies for treating various diseases and disorders [7].…”

<i>In Situ</i> Hydrogel Formulation for Intra-Articular Application of Diclofenac Sodium-Loaded Polymeric Nanoparticles

“…Since DS has pH dependent solubility such as 0.14 mg DS is soluble in 1 mL of pH 5.8 phosphate buffer and 5.15 mg DS soluble in 1 mL pH 7.4 phosphate buffer at 23±2°C, 29 a pH value which DS is less soluble in the external phase was selected in order to increase encapsulation efficiency. 22 Lowering the external pH from 7.4 to 5.8 (F4) resulted with an increase on encapsulated DS by 32% and from this point on all other nanoparticle formulations (F5 and F6) were prepared with pH 5.8 external phase which allows less DS escape to outer aqueous phase depending on less solubility.…”