Posted November 10, 2015 by admin in Health Technology and Medicine | 327 Total Views
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CRYSTAL ENGINEERING TO IMPROVE THE SOLUBILITY AND DISSOLUTION RATE OF NIMODIPINE

sundani fa
sundani fa
Improving the solubility of drugs is currently one of the main challenges for the pharmaceutical industry. There has been growing interests in the design of pharmaceutical cocrystals, which emerges as a potential method for enhancing the bioavailability of drugs with low aqueous solubility. Cocrystal approach is a method of great interest for the pharmaceutical industry. Apart from offering potential improvements in solubility, dissolution rate, bioavailability and physical stability, pharmaceutical cocrystals can enhance other essential properties of the APIs such as flowability, chemical stability, compressability and hygroscopicity (Lu danRohani , 2009). Therefore, the co – crystal has a different physical character with the behavior exhibited physical mixture of both components without treatment ( Soewandhi 2005).
Nimodipine (NMP), which is classified as BCS II, is a dihydropyridine calcium channel blocker recommended for the improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in patients with subarachnoid hemorrhage (Langley dan Sorkin , 1989). Until now there has been no product pharmaceutical industry in Indonesia to match the quality of nimodipine tablets innovators.
The aim of this study was to improve the physical properties of nimodipine through crystal engineering and its to increase the solubility and dissolution rate as the initial parameters improved bioavailability . The screening of coformer candidate using cold contact method. Preparation of cocrystal form used solvent evaporation method. Characterized by a polarization microscope, X-ray diffraction, DSC, FTIR and SEM, solubility and dissolution rate test. Based on the screening results with cold contact method was known that isonicotinamide potential to be coformer. Phase diagram was made from the types of interactions that occur. Curve obtained from the phase diagram is congruent curves which indicate that the interaction between the two compounds is the formation of molecular compounds (cocrystal ) at a ratio of 2 : 1 . The PXRD patterns shown nimodipine-isonicotinamide (2:1)cocrystal are different from its physical mixtures and starting components. Solubility test conducted by the flask method for 24 hours. Analysis using HPLC
with a reverse phase C18 column , mobile phase acetonitrile – water (70:30). Regression equation y = 50030x – 20560 with the value of r2 = 0.9996 . Retrieved increase the solubility of nimodipine from 0959 ± 0.446μg / ml to 1,771 ± 0.075μg / ml . Dissolution studied were found to enhanced release of the drug from 37.29 % to 50.98 %
CONCLUSION
1. Cocrystal formation between nimodipine – isonicotinamide has been characterized by PXRD, DSC and FTIR. The PXRD patterns shown nimodipine-isonicotinamide (2:1)cocrystal are different from its physical mixtures and starting components. DSC thermograms of nimodipine-isonicotinamide (2:1) cocrytals have unique thermal behavior, which had lower than each pure component.
2. Solubility and dissolution rate nimodipine-isonicotinamide (2:1) cocrystal higher than the pure nimodipine .
LIST OF RESEARCH OUTPUT
1. ”Cocrystal Screening of Nimodipine”, International Seminar on Pharmaceutical Science and Technology (ISPST 2014), Jatinangor, Jawa Barat, Indonesia, 18th-19thSeptember 2014
2. ”Identification of Physical Interaction between Nimodipine and Isonicotinamide by Cold Contact Method and Solvent Evaporation”, The 6th AONSA Neutron School, Celebrating the International Year of Crystallography, Serpong, Banten, Indonesia, 12th – 17th October 2014.
Figure 1. PXRD patterns of nimodipin, isonicotinamide, physical mixture
nimodipin-isonicotinamide (1:1) and nimodipine-isonicotinamide cocrystal
after solvent evaporation with methanol as solvent.
equation y =50030x – 20560 with the value of r2 = 0.9996 . Retrieved increase the solubility of nimodipine from0959 ± 0.446μg / ml to 1,771 ± 0.075μg / ml . Dissolution studied were found to enhanced release ofthe drug from 37.29 % to 50.98 %CONCLUSION1. Cocrystal formation between nimodipine – isonicotinamide has been characterized by PXRD, DSC andFTIR. The PXRD patterns shown nimodipine-isonicotinamide (2:1)cocrystal are different from itsphysical mixtures and starting components. DSC thermograms of nimodipine-isonicotinamide (2:1)cocrytals have unique thermal behavior, which had lower than each pure component.2. Solubility and dissolution rate nimodipine-isonicotinamide (2:1) cocrystal higher than the purenimodipine .LIST OF RESEARCH OUTPUT1. ”Cocrystal Screening of Nimodipine”, International Seminar on Pharmaceutical Science and Technology(ISPST 2014), Jatinangor, Jawa Barat, Indonesia, 18th-19thSeptember 20142. ”Identification of Physical Interaction between Nimodipine and Isonicotinamide by Cold ContactMethod and Solvent Evaporation”, The 6th AONSA Neutron School, Celebrating the International Year ofCrystallography, Serpong, Banten, Indonesia, 12th – 17th October 2014.Figure 1. PXRD patterns of nimodipin, isonicotinamide, physical mixturenimodipin-isonicotinamide (1:1) and nimodipine-isonicotinamide cocrystalafter solvent evaporation with methanol as solvent.
HEAD OF RESEARCH TEAM :
TEAM MEMBERS : Dr. Lucy D.N. Sasongko, Prof. Dr. Ismunandar
OFFICIAL ADDRESS : Lab Farmasetika Sekolah farmasi, Institut Technologi Bandung,
Jl. Ganesha 10 Bandung
EMAIL : sundani@fa.itb.ac.id
Prof. Dr. rer.nat. Sundani Nurono Soewandhi

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