EFFORT TO REDUCE COMPRESSIBILITY OF RAMIPRIL THROUGH CRYSTAL ENGINEERING

• Main Author: Indra
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/45761
• Institution: Institut Teknologi Bandung

In drug development process, one of the early decisions that must be made is determining crystalline forms or polymorphs of the drug. Physical properties of solid polymorphs can influence the quality, safety and efficacy of drug. Considering that the bond can affect the physical properties at the macroscopic level, the efforts to manipulate the physical properties by regulating the molecular re-arrangement in the solid state into a different crystal are things that can be importanc in the pharmaceutical industry. Cocrystal has the physical properties, such as particle size and crystal habit that can influence the surface properties, suspended ability, dissolution rate, the behavior of powder compressibility and compactibility. Mechanical properties are those properties of a material under the influence of an applied stress. Compressibility, tabletability and compactibility are parameters to characterizing the mechanical properties whose are important to produce tablet dosage form. The aim of this study was to reduce the compressibility of ramipril due to formation of cocrystal. The solid phase was characterized by contact methode, a termal methode (Differential Scanning Calorimetry), microscopy (polarizing microscope and Scanning Electron Microscopy), diffractometry (Powder X-Ray Diffraction), solubility test, compressibility, and dissolution test. The result of contact method shown formation of new crystal habit in contact zone (mixing zone) betwen solid ramipril (RA) and vanilline (VA). It had a different melting point than its single componen. Thermogram of DSC indicated a new endothermic peak corresponding to melting point of a new cocrystalline phase at temperature 91.9 o C. New powder X-Ray diffracton (PXRD) interferences peaks at 2?= 6,12; 8,96; 11,88 dan 20,04 were observed in addition to PXRD interference peaks of each component that evidence of formation cocrystalline phase. Solubility test of cocrystal RA- VA (12,823±0,07 mg/mL) increase compare to pure (10,437±0,06 mg/mL) and recrystallized RA (10,829±0,08 mg/mL). Compressibility characterization shown that the compressibility of RA decrease after cocrystallization process with VA. Dissolution test of powder and various compression tablet shown that cocrystal RA-VA has lower dissolution rate compared to pure RA in both medium 0.1 N HCl and phosphate buffer 6.8.