Abstract
The aim of present study was to study the interaction of terbinafine hydrochloride with nicotinamide in solution as well as solid state. Solid dispersions of terbinafine hydrochloride were prepared by fusion method using nicotinamide as carrier in different ratios. Phase solubility studies were carried out at three different temperatures and thermodynamic parameters like enthalpy change (ΔH), entropy change (ΔS) and free energy change (ΔG) were calculated. These formulations were further characterized in the solid state by differential scanning calorimetry, powder X-ray diffraction and Fourier transform infrared spectroscopy. Solubility and dissolution studies showed that nicotinamide increases the solubility and dissolution rate of terbinafine hydrochloride. Thermodynamic parameters and solid state studies confirmed the absence of any chemical interactions between terbinafine hydrochloride and nicotinamide. It is concluded that the mechanism for increase in solubility of terbinafine hydrochloride by nicotinamide is the water breaking properties of nicotinamide.
Similar content being viewed by others
References
Agrawal S, Pancholi SS, Jain NK, Agrawal GP (2004) Hydrotropic solubilization of nimesulide for parenteral administration. Int J Pharm 274:149–155
Ahuja N, Katare OP, Singh B (2007) Studies on dissolution enhancement and mathematical modeling of drug release of a poorly water-soluble drug using water-soluble carriers. Eur J Pharm Biopharm 65:26–38
ArunParsad K, Narayanan N, Rajalakshmi G (2010) Preparation and Evaluation of solid dispersion of Terbinafine Hydrochloride. Intl J Pharm Sci Rev Res 3:130–134
Babu GV, Kumar NR, Himasankar K, Seshasayana A, Murthy KV (2003) Nimesulide-modified gum karaya solid mixtures: preparation, characterization and formulation development. Drug Dev Ind Pharm 29:855–864
Coffman RE, Kildsig DO (1996a) Hydrotropic solubilization–mechanistic studies. Pharm Res 13:1460–1463
Coffman RE, Kildsig DO (1996b) Effect of nicotinamide and urea on the solubility of riboflavin in various solvents. J Pharm Sci 85:951–954
El-Gazayerly ON (2000) Characterization and evaluation of tenoxicam coprecipitates. Drug Dev Ind Pharm 26:925–930
Higuchi T, Connors KA (1965) Phase solubility techniques. Adv Anal Chem Instrum 4:117–212
Hussain MA, DiLuccio RC, Maurin MB (1993) Complexation of moricizine with nicotinamide and evaluation of the complexation constants by various methods. J Pharm Sci 82:77–79
Jain NK, Singhai AK, Jain S (1996) Hydrotropic solubilization of ketoprofen. Die Pharmazie 51:236–239
Kumar N, Jain AK, Singh C, Kumar R (2008) Development, characterization and solubility study of solid dispersion of terbinafine hydrochloride by solvent evaporation method. Asian J Pharm 2:154–158
Kushida I, Ichikawa M, Asakawa N (2002) Improvement of dissolution and oral absorption of ER-34122, a poorly water soluble dual 5-lipoxygenase/cyclooxygenase inhibitor with anti-inflammatory activity by preparing solid dispersion. J Pharm Sci 91:258–266
Lim LY, Go ML (2000) Caffeine and nicotinamide enhances the aqueous solubility of the antimalarial agent halofantrine. Eur J Pharm Sci 10:17–28
Margarit MV, Rodriguez IC, Cerezo A (1994) Physical characteristics and dissolution kinetics of solid dispersions of ketoprofen and polyethylene glycol 6000. Int J Pharm 108:101–107
Modi A, Tayade P (2006) Enhancement of Dissolution Profile by Solid Dispersion (Kneading) Technique. AAPS Pharm Sci Tech 7:E87–E92
Murali Mohan Babu GV, Prasad CHDS, Ramana Murthy KV (2002) Evaluation of modified gum karaya as carrier for the dissolution enhancement of poorly water soluble drug nimodipine. Int J Pharm 234(1–2):1–17
Newa M, Bhandari KH, Oh DH, Kim YR, Sung JH, Kim JO, Woo JS, Choi HG, Yong CS (2008) Enhanced dissolution of ibuprofen using solid dispersion with poloxamer 407. Arch Pharm Res 31(11):1497–1507
Okonogi S, Yonemochi E, Oguchi T, Puttipipatkhachorn S, Yamamoto K (1997) Enhanced dissolution of ursodeoxycholic acid from the solid dispersion. Drug Dev Ind Pharm 23:1115–1121
Rassol AA, Hussain AA, Dittert LW (1991) Solubility enhancement of some water-insoluble drugs in the presence of nicotinamide and related compounds. J Pharm Sci 80:387–393
Rogers JA, Anderson AJ (1982) Physical characteristics and dissolution profiles of ketoprofen-urea solid dispersions. Pharm Acta Helv 57:276–281
Sanghvi R, Evans D, Samuel H, Yalkowsky (2007) Stacking complexation by nicotinamide: a useful way of enhancing drug solubility. Int J Pharm 336(1):35–41
Shahjahan M, Enever RP (1992) Investigation of the nature of the interaction of nitrofurazone with urea. Int J Pharm 82:229–232
Sudha RV, Zeren W, Stefanie H, Steven LK (2007) Factors affecting the formation of eutectic solid dispersions and their dissolution behavior. J Pharm Sci 96:294–304
Suzuki H, Sunada H (1998) Influence of water-soluble polymerson the dissolution of nifedipine solid dispersions with combined carriers. Chem Pharm Bull 46(3):482–487
Torrado S, Torrado S, Torrado JJ, Cadorniga R (1996) Preparation, dissolution and characterization of albendazole solid dispersions. Int J Pharm 140:247–250
Truelove J, Bawarshi-Nassar R, Chen NR, Hussain A (1984) Solubility enhancement of some developmental anticancer nucleoside analogs by complexation with nicotinamide. Int J Pharm 19:17–25
Varma MM, Pandi JK (2005) Dissolution, solubility, XRD and DSC studies on Flurbiprofen- Nicotinamide solid dispersions. Drug Dev Ind Pharm 31:417–423
Verheyen S, Blaton N, Kinget R, Van den Mooter G (2002) Mechanism of increased dissolution of diazepam and temazepam from polyethylene glycol 6000 solid dispersions. Int J Pharm 249:45–58
Vippagunta SR, Maul KA, Tallavajhala S, Grant DJW (2002) Solid-state characterization of nifedipine solid dispersions. Int J Pharm 236:111–123
Yagi N, Terashima Y, Kenmotsu H, Sekikawa H, Takada M (1996) Dissolution behavior of probucol from solid dispersion systems of probucol-polyvinylpyrrolidone. Chem Pharm Bull 44:241–244
Acknowledgments
This article does not contain any studies with human and animal subjects performed by any of the authors. All authors (AK Aggarwal, P. Jindal) declare that they have no conflict of interest. We are grateful to FDC Pvt. Ltd., Mumbai, India for their interest and supply of gift sample of terbinafine hydrochloride.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Aggarwal, A.K., Jindal, P. Interaction of terbinafine hydrochloride with nicotinamide in solution and solid state. Journal of Pharmaceutical Investigation 44, 23–32 (2014). https://doi.org/10.1007/s40005-013-0097-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40005-013-0097-9