Research Journal of Pharmacy and Technology

Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

A Novel Co-crystallization Technique to Enhance the Physicochemical Property of Bcs Class-ii Drugs Using Efavirenz as a Model Drug


Affiliations
1 Government College of Pharmacy, Karad, Dist.– Satara – 415004 Maharashtra,, India
2 Government College of Pharmacy, Ratnagiri, 415612, Maharashtra, India
3 Global College of Pharmacy, Moinabad, R.R. Dist., Telangana State, 501504, India
     

   Subscribe/Renew Journal


Pharmaceutical co-crystallization, a novel technique, provides for alteration and tailoring of physicochemical properties of active pharmaceutical ingredients (API) notwithstanding maintaining the intrinsic activity of the drug molecule. In the present work, co-crystals of efavirenz (EFA) were prepared with selected conformers of GRAS (Generally Recognized as Safe) status wise salicylic acid (SA) and benzoic acid (BA) using solution crystallization method to improve its dissolution. The assembly of crystal structure was evaluated by means of fourier transformation infrared spectroscopy (FTIR), x-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and nuclear magnetic resonance (NMR). Saturation solubility and in vitro dissolution studies were further employed to investigate co-crystals. Equilibrium solubility profile of EFA-SA and EFA-BA exhibits an enhancement of 1.60 and 1.29 folds of solubility of efavirenz co-crystals as compared to the pure drug. Pharmacokinetic study performed in rats showed AUC0-∞ for co-crystals formulation was higher (13.15±0.02μg hmL−1) than the pure drug suspension formulation 7.85±0.03μg hmL−1. Statistically, AUC0-t of the co-crystal formulation was significantly higher (p<0.05) as compared to pure drug suspension formulation. Higher amount of drug concentration in blood indicated better systemic absorption of efavirenz from co-crystals formulation as compared to the pure drug suspension formulation.


Keywords

Pharmaceutical co-crystallization, Physicochemical properties, Co-crystals, Aqueous solubility.
Subscription Login to verify subscription
User
Notifications
Font Size


  • Samineni R. Chimakurthy J. Sumalatha K. Dharani G. Rachana J. Manasa K. Anitha P. Co-Crystals: A review of recent trends in co crystallization of BCS class II drugs. Research Journal of Pharmacy and Technology 2019; 12(7): 3117-3124. doi: 10.5958/0974-360X.2019.00527.4

  • Almarsson O. Zaworotko MJ. Crystal engineering of the composition of pharmaceutical phases. Do pharmaceutical co-crystals represent a new path to improved medicines?. Chemical Communications. 2004; 17: 1889-1896. doi: 10.1039/b402150a

  • Nair A. Harini R. Melissa P. Shah K. Nayak UY. Mahalaxmi R. Vamshi KT. Development and characterization of Irbesartan Co-Crystals. Research Journal of Pharmacy and Technology. 2018; 11(9): 3932-3936.doi: 10.5958/0974-360X.2018.00722.9

  • Jagtap S. Magdum C. Jadge D. Jagtap R. Solubility Enhancement Technique: A Review. Journal of pharmaceutical science and research.2018; 10(9):2205-2211.

  • Gardner CR. Walsh CT. Almarsson O. Drugs as materials: Valuing physical form in drug discovery. Nature Reviews Drug Discovery. 2004; 3(11): 926–934. doi: 10.1038/nrd1550

  • Zalte AG. Saudagar RB. Preparation and characterization of etodolac co-crystals using 32 full factorial design. Research Journal of Pharmacy and Technology. 2018; 11(9): 3781-3786.doi:10.5958/0974-360X.2018.00693.5

  • Thomas JE. Nayak UY. Jagadish PC. Koteshwara KB. Design and characterization of valsartan co-crystals to improve its aqueous solubility and dissolution behavior. Research Journal of Pharmacy and Technology. 2017; 10(1): 26-30. doi: https://doi.org/10.5958/0974-360X.2017.00007.5

  • Schultheiss N. Newman A. Pharmaceutical co-crystals and their physicochemical properties. Crystal Growth and Design. 2009; 9(6): 2950-2967. doi: https://doi.org/10.1021/cg900129f

  • Damiani A. De Santis P. Giglio E. Liquori AM. Puliti R. Ripamonti A. The crystal structure of the 1:1 molecular complex between 1,3,7,9- tetramethyluric acid and pyrene. Acta Crystallographica. 1965; 19: 340-348. doi: https://doi.org/10.1107/S0365110X65003420.

  • Jagtap RS. Doijad RC. Mohite SK. Adsorption of nifedipine on porous calcium silicate for enhancement of solubility and dissolution rate. Research J. Pharm. and Tech. 2019; 12(3): 1273-1279. doi: 10.5958/0974-360X.2019.00213.0

  • Buguet A. Cryoscopy of Organic Mixtures and Addition Compounds. Comptes Rendus Chimie. 1910; 149: 857-858.

  • Grossmann H. Thiourea. Chemiker-Zeitung. 1908; 31: 1195-1196.

  • Pekker S et al. Rotor-stator molecular crystals of fullerenes with cubane. Nature Materials. 2005; 4: 764-767.

  • Zalte AG. Saudagar RB. Preparation and characterization of flurbiprofen co-crystals by using factorial design. Asian Journal of Research in Chemistry. 2018; 11(1): 166-170. doi: 10.5958/0974-4150.2018.00034.2

  • Daingade CS. Jain BU. Kondawar M. Pharmaceutical Co-Crystalization: A Review. Research Journal of Pharmaceutical Dosage Forms and Technology. 2019; 11(2): 143-146. doi: 10.5958/0975-4377.2019.00024.7

  • Sevukarajan M. Bachala T. Sodanapalli R. Nair R. Co-Crystals: an emerging trend in pharmaceutical industry. Research Journal of Pharmacy and Technology. 2011; 4(6): 891-902.

  • Garbacz P. Paukszta D. Sikorski A. Wesolowski M. Structural characterization of co-crystals of chlordiazepoxide with p- aminobenzoic acid and lorazepam with nicotinamide by DSC, X-ray Diffraction, FTIR and raman spectroscopy. Pharmaceutics. 2020; 12(7): 648. doi: https://doi.org/10.3390/pharmaceutics12070648

  • Mali SS. Killedar SG. To enhance the physicochemical properties of metoprolol succinate by co-crystal technique. Research Journal of Pharmacy and Technology. 2017; 10(11): 3761-3767.doi: 10.5958/0974-360X.2017.00683.7

  • Parvin ZM. Mohammad BJ. Mandana A. Hadi V. Biopharmaceutical classification of drugs using intrinsic dissolution rate (IDR) and rat intestinal permeability. European Journal of Pharmaceutics and Biopharmaceutics. 2009; 73: 102-106.doi: 10.1016/j.ejpb.2009.04.015

  • Tamilselvi N. Arivukkarasu R. Shahanas SR. Jayan SS. Development and validation of HPTLC method for the determination of efavirenz in tablet dosage form. Research Journal of Pharmacy and Technology. 2018; 11(3): 885-888.doi: 10.5958/0974-360X.2018.00169.5

  • Takano R. Sugano K. Higashida A. Hayashi Y. Machida M. Aso Y. Yamashita S. Oral absorption of poorly water-soluble drugs: computer simulation of fraction absorbed in humans from a miniscale dissolution test. Pharmaceutical Research. 2006; 23(6): 1144-1156.doi: 10.1007/s11095-006-0162-4

  • Craig DQM. The mechanisms of drug release from solid dispersions in water-soluble polymers. International Journal of Pharmaceutics. 2002; 231(2): 131-144.doi: 10.1016/s0378-5173(01)00891-2

  • Gupta S. Kesarla R. Chotai N. Omri A. Development and validation of reversed-phase HPLC gradient method for the estimation of efavirenz in plasma. PLoS ONE. 2017; 12(5): e0174777.doi: 10.1371/journal.pone.0174777.

  • Higuchi T. Connors KA. Phase solubility techniques. Advanced Analytical Chemistry and Instrumentation. 1965; 4: 117-212.


Abstract Views: 139

PDF Views: 0




  • A Novel Co-crystallization Technique to Enhance the Physicochemical Property of Bcs Class-ii Drugs Using Efavirenz as a Model Drug

Abstract Views: 139  |  PDF Views: 0

Authors

Vikram R. Shinde
Government College of Pharmacy, Karad, Dist.– Satara – 415004 Maharashtra,, India
Yogesh V. Pore
Government College of Pharmacy, Ratnagiri, 415612, Maharashtra, India
J. Venkateshwara Rao
Global College of Pharmacy, Moinabad, R.R. Dist., Telangana State, 501504, India

Abstract


Pharmaceutical co-crystallization, a novel technique, provides for alteration and tailoring of physicochemical properties of active pharmaceutical ingredients (API) notwithstanding maintaining the intrinsic activity of the drug molecule. In the present work, co-crystals of efavirenz (EFA) were prepared with selected conformers of GRAS (Generally Recognized as Safe) status wise salicylic acid (SA) and benzoic acid (BA) using solution crystallization method to improve its dissolution. The assembly of crystal structure was evaluated by means of fourier transformation infrared spectroscopy (FTIR), x-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and nuclear magnetic resonance (NMR). Saturation solubility and in vitro dissolution studies were further employed to investigate co-crystals. Equilibrium solubility profile of EFA-SA and EFA-BA exhibits an enhancement of 1.60 and 1.29 folds of solubility of efavirenz co-crystals as compared to the pure drug. Pharmacokinetic study performed in rats showed AUC0-∞ for co-crystals formulation was higher (13.15±0.02μg hmL−1) than the pure drug suspension formulation 7.85±0.03μg hmL−1. Statistically, AUC0-t of the co-crystal formulation was significantly higher (p<0.05) as compared to pure drug suspension formulation. Higher amount of drug concentration in blood indicated better systemic absorption of efavirenz from co-crystals formulation as compared to the pure drug suspension formulation.


Keywords


Pharmaceutical co-crystallization, Physicochemical properties, Co-crystals, Aqueous solubility.

References