Abstract

Current research work cracks to determine one of the imp concerns related to the design and development of prolonged-release spherule of metformin for oral preparations, personalized to treat high blood glucose level. For same, in the Design of Experiments (DOE) an arbitrary interface, “Coating Efficiency” (CE) is well planned and topped the Cumulative Percentage Coating (CPC) to get anticipated control over drug release (DR). Subsequently, the granules containing metformin are converted to spherules and then to Hydroxypropyl Methylcellulose K-15 (HPMC) Coated Spherules (CS) by a novel Cradle Coating during the Rolling (CCDR) process. Among spherules, one with 0.35 mm than 0.71 mm shows required properties. The CS has a low 1200 angle by Optical Microscopy (OM), smooth surface without cracks by Scanning Electron Microscopy (SEM), and better flow properties (Angle of repose 29.69 ± 0.780 , Carr's index 6.73 ± 2.24%, Hausner's Ratio 1.07 ± 0.03) than granules and spherules. Once certain structure-dependent control over release is attained (HPMC coated spherules shows 10% reduction in Burst Release (BR) than uncoated spherules showing a release of 80–91%) the predictability is achieved and Design of Space (DOS) by DOE (CE-70.14% and CPC-200% and DR61.54%) is established. The results of DOE to experimentally validated results were within 20% deviation. The Metformin is changing its crystal structure by powder X-ray Diffraction (PXRD) and Differential Scanning Calorimetry (DSC) from Form-I to Form-II showing polymorphism inside the drug reservoir with respect to the process. This CE and CPC approach in DOE can be used for delivery system design of other labile drugs similar to metformin in crisis situations.

Keywords

Diabetes Mellitus; Hydroxypropyl methylcellulose K-15; Metformin; Spherules

Introduction