*Corresponding Author: D. Ravi Sankara Reddy, Assistant Professor, Department of Pharmaceutical Chemistry, University College of Pharmaceutical Sciences, Acharya Nagarjuna University, Guntur (AP), India.
Sacubitril and valsartan are prescribed for symptomatic heart failure in pediatric patients, but currently marketed film-coated tablets require triturating and mixing with food before administration. This leads to poor acceptability and may compromise accurate dose delivery. To address this limitation, the present study plans to develop HPMC-coated sacubitril-valsartan microspheres via spray drying and to formulate them into a reconstituted oral suspension to demonstrate equivalence to the marketed products (F1 and F2) and to improve pediatric patient acceptance and accurate dose delivery.
Sacubitril, valsartan, and HPMC were dissolved in a hydroalcoholic system (water: ethanol, 80:20% v/v) at drug–polymer concentrations of 50–300 micrograms per millilitre, where the solution was maintained at a temperature of 2-8°C to minimise ethanol loss. The mixture was vortexed, then homogenised at 15,000 rpm, and subsequently spray-dried under optimised conditions. The microspheres were analysed for drug content, particle size, morphology, residual solvents, moisture content, and in vitro release.
The formulations exhibited high encapsulation efficiency (50–70%) and produced spherical microspheres with a wrinkled surface. Particle size observed as D10 500 µm, D50 1120 µm, and D90 2280 µm, with a Z-average of 1300 nm, a PDI of 0.298, and a Span of 1.58, as determined using a Malvern Zetasizer. In vitro studies demonstrated enhanced drug release, influenced by the extent of polymer cross-linking.
For the oral suspension formulation, 100 mg of sacubitril and valsartan HPMC-coated microspheres (equivalent to 50 mg sacubitril and 50 mg valsartan), sucrose (477 mg), mannitol (339 mg), disodium edetate (8 mg), sodium metabisulfite (1 mg), HPC (7 mg), and orange flavour (70 mg) were added. To form a uniform blend, all components were mixed and sieved through a 24 mesh.
Conclusion: Spray-dried HPMC-coated microspheres showed favourable physicochemical properties and improved release behaviour, indicating their potential as a pediatric-friendly oral delivery system for sacubitril–valsartan therapy.
Keywords: Sacubitril, Valsartan, Spray drier, Microspheres, Zetasizer, HPLC, SEM, Gas Chromatography, Karl Fischer titration, In vitro release.
How to cite this article: Sivaram B, Reddy DRS. Development and evaluation of spray-dried HPMC-coated sacubitril–valsartan microspheres for oral delivery in pediatric patients. Int J Drug Deliv Technol. 2026;16(6s): 193-204; DOI: 10.25258/ijddt.16.6s.25
Source of support: Nil.
Conflict of interest: None