Formulation Of Metformin-gliclazide Nano Cocrystals For The Management Of Type-2 Diabetes Mellitus

• By: CHIDZIWA, Tinotenda (Sefako Makgatho Health Science University, South Africa)
• Co-author(s): Ms Tinotenda Chidziwa (Sefako Makgatho Health Science University, Pretorial, South Africa)
  
• Abstract:

  Formulation of Metformin-Gliclazide Nano Cocrystals for the Management of Type-2 Diabetes Mellitus
  *TV Chidziwa1, V Smith2 and BA Witika1
  1Department of Pharmaceutical Sciences, School of Pharmacy, Sefako Makgatho Health Sciences University, South Africa
  2Department of Chemistry, Faculty of Science, Rhodes University, South Africa E-mail address: [email protected]
  BACKGROUND AND OBJECTIVES:
  Pharmaceutical Nano cocrystals (NCC) are aimed at improving drug properties such as stability, mechanical properties, and bioavailability. The formulation of a NCC is an advanced strategy that uses the top-down and bottom-up formulation techniques. They have the potential of enhancing the physicochemical properties of the drugs. NCCs are nanometre-scale pharmaceutical cocrystals that exhibit properties that are superior to those of co-crystals and nanocrystals. NCC combination of nano sizing and cocrystallization is utilized in their formation further enhancing bioavailability, solubility, hygroscopicity, and dissolution kinetics. In this study, we report the results obtained from the formulation of metformin-gliclazide nano cocrystals by top down and bottom up methods. The aim of the study is to synthesize a novel metformin-sulfonylurea NCC-loaded microneedle array for the management of T2DM.
  METHODS:
  The metformin base was extracted from metformin HCL by reacting metformin HCL and sodium hydroxide. Metformin-gliclazide nano cocrystal were developed using a pseudo one solvent bottom-up method. Equimolar amounts of metformin were dissolved in deionized water and gliclazide in acetone were injected rapidly into a precooled polytube and sonicated at temperatures between 3-5°. The nano cocrystal suspension was first characterized using a zetasizer. The particle size,poly dispersity index and zeta potential were detertimed. The suspension was dried and subsequently characterized using the powder Xray diffraction, differential scanning calorimetry scanning electron microscopy and Fourier transform infrared spectroscopy. Surfactants that include tween 80, span 80, poloxamer 188, p407, pluronic 127 and TPGS were utilized as stabilizers for the for-mulation.
  RESULTS:
  The results indicated the presence of a possibility of a nano-cocrystal with metformin- gliclazide. The metformin-gliclazide nano-co-crystal analysis with the XRD exhibited the disappearance of characteristic peaks of gliclazide and metformin and the appearance of novel characteristic peaks. The FTIR spectrum indicated bond shifts in -OH groups and -NH groups indicating the probability of hydrogen bond formation and enhancement of the conjugative effect. The DSC data reflected changes in melting point onset, enthalpy energies and the existence of single melting points.
  CONCLUSION: The screening results of the study showed that gliclazide exhibited a nanococrystal profile that could potentially be utilized in drug-drug pharmaceutical nano cocrystal combinations.