Preparation and characterization of Benzathine Penicillin G solid dispersions using different hydrophilic carriers
Keywords:
Benzathine benzylpenicillin G, Solid Dispersion, HPMC, PVP K30, PEG4000, MannitolAbstract
Several technical factors related to penicillin G intramuscular injection can affect its bioavailability and hence reduce the efficacy of rheumatic fever prevention program. When small amount of diluent is used, the powder is not completely dissolved and the thick suspension frequently causes obstruction of injection needle. The study aimed to characterize the solid-state properties of solid dispersion systems of benzathine penicillin G (BPG) prepared with hydrophilic carriers by applying solvent evaporation method. The results of spectroscopic studies; Fourier transform-infra red (FTIR), Nuclear Magnetic Spectroscopy (1HNMR) and Differential Scanning Calorimetry (DSC) revealed no chemical interaction between the drug and carriers. No significant changes in drug crystalline state were observed by X-ray diffraction and Scanning Electron Microscope (SEM) studies, even with using amorphous carriers; polyvinyl pyrrolidone (PVP-K30) and hydroxypropyl methylcellulose (HPMC). All the prepared solid dispersions demonstrated 76-93% yield and % drug content dependent on the polymer type and concentration. The hydrophilic polymers demonstrated potential effect on improving the flowability, wettability and dissolution characters of the drug. The results revealed that it is possible to enhance the dissolution rate of BPG (hydrophobic drug) by increasing the surface area of the drug adsorbed on the surface of hydrophilic polymer by solid dispersion method. Finally, solid dispersion BPG: PEG 4000 at ratio 50:50 gave uniform flowability of the powder (around 30), wettability (12 min) and faster dissolution rates among all the formulations. Thus, it was selected as the best formulation in this study.
References
Miller EL. The penicillins: A review and update. J Midwifery Women Health. 2002; 47: 426-434.
. Gerber MA. So what’s wrong with penicillin for strep throat? Pediatrics. 2004;113:1816-1819.
. Kassem AS, Zaher SR, Abou Shleib H, El-Kholy AG, Madkour AA, Kaplan EL. Rheumatic fever prophylaxis using benzathine penicillin G (BPG): two- week versus four week regimens: comparison of two brands of BPG. Pediatrics. 1996;97: 992-995.
. Carapetis JR, Currie BJ, Mathews JD. Cumulative incidence of rheumatic fever in an endemic region: a guide to the susceptibility of the population. Epidemiol Infect. 2000;13:239-244.
. Peloso UC, De Souza JC, Botino MA, Miniti A. Penicillin concentrations in sera and tonsils after intramuscular administration of benzathine penicillin G to children. Pediatr Infect Dis J. 2003;22:1075-1078.
. Amir J, Ginat S, Cohen Y H, Marcus T E, Kehher N, Varsano I. Lidocaine as a diluent for administration of benzathine penicillin G. Pediatr Infec Dis J. 1998;17: 890-893.
. Santos MNS, Pontes A, Pereira VMW, Caetano MNP. Colloidal carriers for benzathine penicillin G: nanoemulsions and nanocapsules. Int J Pharm 2000;208:71-80.
. Holanda E, Silva KG, Xavier J. FH, Farias, IEG, Caldas NJA, Silva AKAS, Nakashima JT. A new insight about pharmaceutical dosage forms for benzathine penicillin G. Rev Cienc Farm Basica Apl. 2006;27:21-26.
. Swarbrick J. Encyclopedia of Pharmaceutical Technology. 6th ed. New York: Marcel Dekker, 1990. p. 31-63.
. Craig, DQM. The mechanism of drug release from solid dispersions in water-soluble polymers. Int J Pharm. 2001;231:131-144.
. Serajuddin ATM. Solid dispersion of poorly water soluble drugs: early promises, subsequent problems and recent breakthroughs. J Pharm Sci. 1999; 881058-1066.
.Yamashita K, Nakate T, Okimoto K, Ohike A, Tokunaga Y, Ibuki R. Establishment of new preparation method for solid dispersion formulation of tacrolimus. Int J Pharm. 267, 79-91, 2003.
. Shivalingam BMR, Kishore RYV, Rao S, Rajesh K, Sunitha N. Formulation and evaluation of aceclofenac solid dispersions for dissolution rate enhancement. Int J Pharm Sci Drug. Res. 2010;2:146-150.
. Yamashita K, Nakate T, Okimoto K, Ohike A, Tokunaga Y, Ibuki R, Higaki K, Kimura T. Establishment of new preparation method for solid dispersion formulation of tacrolimus. Int J Pharm. 2003;267: 79-91.
. Teeranachaideekul V, Junyaprasert VB, Souto E B, Muller R H. Development of ascorbyl palmitate nanocrystals applying the nanosuspension technology. Int J Pharm. 2007;354: 227-234.
. Liu X, Lin H, Thenmozhiyal JC, Chan S, Paul HC. Inclusion of acitretin into cyclodextrins: phase solubility, photostability and physicochemical characterization. J Pharm Sci. 2003;92: 2449-2457.
. Rajesh A, Singeeta A, Lamba HS, Bhandari A, Sadeep K. The effect of the preparation of solid dispersion method on the solubility and crystallinity of sulfasalazine. Int Res J Pharm. 2011;2:200-206.
. Singh A, Sharma PK, Meher JG, Malviya R. Evaluation of Enhancement of solubility of paracetamol dispersion technique using polymer concentration flow properties. Asian J Pharm Clin Res. 2011;4:117-119.
. Raghavendra RNG, Kulkarni U, Setty CM. Comparative Study on Effect of different techniques used in the formulation of felodipin fast dissolving tablet. Int J Pharm Sci. 2010;2:152-159.
