Comprimidos mucoadherentes bicapa para la administración bucal de carvedilol: Estudios in vitro e in vivo

  • PD YEDURKAR Drug Delivery Research Laboratory, TIFAC Center of Relevance and Excellence in NDDS, G. H. Patel Building, Pharmacy Department, Faculty of Tech. and Engg., The M. S. University of Baroda, Vadodara – 390 002, Gujarat, India.
  • MK DHIMAN Drug Delivery Research Laboratory, TIFAC Center of Relevance and Excellence in NDDS, G. H. Patel Building, Pharmacy Department, Faculty of Tech. and Engg., The M. S. University of Baroda, Vadodara – 390 002, Gujarat, India.
  • KK SAWANT Drug Delivery Research Laboratory, TIFAC Center of Relevance and Excellence in NDDS, G. H. Patel Building, Pharmacy Department, Faculty of Tech. and Engg., The M. S. University of Baroda, Vadodara – 390 002, Gujarat, India.
Palabras clave: Comprimidos mucoadherentes bicapa, Carvedilol

Resumen

Se diseñó un sistema mucoadherente bicapa de carvedilol para administración bucal, con el objetivo de mejorar labiodisponibilidad y conseguir una liberación sostenida. Como portadores se utilizaron Carbopol 934P e hidroxipropilmetilcelulosaK4M, y las formulaciones obtenidas se sometieron a estudios de pH superfi cial, índice de expansióny bioadhesión y liberación de fármaco in vitro. Se analizó la cinética de los datos de liberación de fármaco in vitro,mediante ajuste en modelos de orden cero, primer orden, Higuchi, Hixson-Crowell y Korsmeyer Peppas. El estudiodel rendimiento farmacocinético in vivo del lote optimizado se realizó en conejos. Los datos obtenidos de la optimizacióny evaluación del sistema revelaron que las formulaciones presentaban índices de expansión y parámetrostecnológicos satisfactorios. La formulación F5 presentó el mayor grado de bioadherencia (3.5 ± 0.6 N) y su retenciónen la mucosa bucal porcina fue de 7 h. El ajuste al modelo de los datos de liberación in vitro demostró que seguíanun patrón de liberación de orden cero con un comportamiento de liberación no Fickian, es decir, con valores de nentre 0.71 y 1.17, lo que indica que la liberación fue una combinación de erosión del comprimido y difusión desdela matriz. Los valores farmacocinéticos obtenidos presentaron una diferencia signifi cativa entre Cmax, Tmax y losvalores del área bajo la curva de las formulaciones bucal y oral, es decir, un aumento de la biodisponibilidad enlos comprimidos bucales en comparación con la formulación oral. Las curvas de concentración en plasma de loscomprimidos bucales evidenciaron claramente un comportamiento de liberación sostenido.

Citas

Parvez N, Ahuja A, Khar RK. Development and evaluation of muco-adhesive buccal tablets of lignocaine hydrochloride.

Ind J Pharm Sci 2002; 64: 563-567.

Rathbone M, Drummond B, Tucker B. The oral cavity as a site for systemic drug delivery. Adv Drug Deli Rev 1994; 13: 1-22.

Squier CA, Wertz PW. Structure and function of the oral mucosa and implications for drug delivery. in Rathbone MJ: (eds). Oral Mucosal Drug Delivery. Marcel Dekker. INC. New York. pp 1-26.1996.

Nagai T, Konishi R. Buccal/gingival drug delivery systems, J Control Rel. 1987; 6: 353-360.

Ishida M, Nambu N, Nagai T. Ointment type oral mucosal dosage forms of carbopol containing prednisolone for treatment of aphtha. Chem Pharm Bull 1983; 31: 1010-1014.

Gurny R, Meyer JM, Peppas NA. Bioadhesive intra oral release system: design, testing and analysis. Biomaterials 1984; 5: 336-340.

Ponchel G, Touchard F, Duchene D, Peppas NA. Bioadhesive analysis of controlled-release systems: I Fracture and interpretation analysis in poly (acrylic acid) containing systems. J Control Rel 1987; 5:129-141.

Berthold A, Cremer K, Kreuter J. Preparation and characterization of chitosan microspheres as drug carrier for prednisolone sodium phosphate as model for anti-inflammatory drugs. J Control Rel 1996; 39:17-25.

Voorspoels J, Remon JP, Eechaute W, DeSy W. Buccal absorption of testosterone and its esters using a bioadhesive tablet in dogs. Pharm Res 1996; 13: 1228–1232.

Senel S, Ikinci G, Kas S, Yousefi-Rad A, Sargon MF, Hıncal AA. Chitosan films and hydrogels of chlorhexidine gluconate for oral mucosal delivery. Int J Pharm 2000; 193: 197–203.

Mumtaz AM, Ch’ng HS. Evaluation of bioadhesive buccal tablets containing triamcinolone acetonide in healthy volunteers. Int J Pharm 1995; 121: 249-254.

Llabot JM, Manzo RH, Allemandi DA. Double-layered mucoadhesive tablets containing nystatin. AAPS PharmSciTech, 2002; 3: article 22.

Tripathi KD. Antiadrenergic drugs (adrenergic receptor antagonists), in: (eds). Essentials of Medical Pharmacology. 4th ed., Jaypee Publishers, New Delhi, pp 131.1999.

Ruffolo RR, Gellai M, Heible JP, Willette RN, Niicholas AJ. The pharmacology of carvedilol. Eur J Clin Phrmacol 1990; 38: S 82.

Nafee NA, Ismail FA, Boraie NA, Mortada LM. Mucoadhesive delivery systems II - Formulation and in-vitro/invivo evaluation of buccal mucoadhesive tablets containing water-soluble drugs. Drug Dev Ind Pharm 2004; 30: 995–1004.

Shojaei H, Paulson J, Honary S. Evaluation of poly (acrylic acid-co-ethylhexyl acrylate) films for mocoadhesive transbuccal drug delivery: factors affecting the force of mucoadhesion. J Control Rel 2000: 67: 223-232.

Oliviera AG de, Giacomelli FC, Giacomelli C, Spinelli A. Microstructure and surface composition effects on the

transpassivation of NiTi wires for implant purposes. J Braz Chem Soc 2005; 16: 131-138.

Dortunc B, Ozer L, Uyanik N. Development and in vitro evaluation of a buccoadhesive pindolol formulation. Drug Dev Ind Pharm 1998; 24: 281-188.

Costa P, Lobo JSM. Modeling and comparison of dissolution profile. Eur J Pharm Sci 2001; 13: 123-133.

Miyazaki S, Nakayama A, Oda M, Takada M, Attwood M Drug release from mucosal adhesive tablets of chitosan and sodium alginate, Int J Pharm 1995; 118: 257-263.

Hokama N, Hobara N, Kameya H, Ohshiro S, Sakanashi M. Rapid and simple micro-determination of carvedilol in rat plasma by high-performance liquid chromatography. J Chrom B, 1999; 732: 233–238.

Repka MA, Prodduturi S, Munjal M, Mididoddi P. Matrix and reservoir based transmucosal delivery systems: tailoring delivery solutions. Am J Drug Deli, 2004; 2: 173-192.

Huntsberger JR. Surface energy, wetting and erosion. J. Adhesion 1971; 6: 11-14.

Salamat-Miller N, Chittchang M, Johnston TP. The use of mucoadhesive polymers in buccal drug delivery. Adv Drug

Deli Rev 2005; 57: 1666– 1691.

Mahaguna V, Talbert RL, Peters JI. Influence of hydroxypropyl methylcellulose polymer on in vitro and in vivo performance of controlled release tablets containing alprazolam. Eur J Pharm Biopharm 2003;56:461-468.

Panomsuk SP, Hatanaka T, Aiba T, Katayama K, Koizumi T. A study of the hydrophilic cellulose matrix: effect of drugs on the swelling properties. Chem Pharm Bull 1996;44: 1039– 1042.

Grabovac V, Guggi D, Bernkop-Schnurch A. Comparison of the mucoadhesive properties of various polymers. Adv Drug Deli Rev 2005; 57: 1713– 1723.

Peh KK, Wong CF. Polymeric films as vehicle for buccal delivery: swelling, mechanical and bioadhesive properties. J Pharm Pharm Sci 1999; 2: 53-61.

Desai KGH, Pramodkumar TM. Preparation and evaluation of a novel buccal adhesive system. AAPS PharmSciTech 2004; 5: Article 35.

Agarwal V, Mishra B. Design, development, and biopharmaceutical properties of buccoadhesive compacts of pentazocine. Drug Dev Ind Pharm 1999; 25: 701-709.

Ritger PL, Peppas A. A simple equation for description of solute release. II. fickian and anomalous release from swellable devices. J Control Rel 1987; 5: 37-42.

Jug M, Becirevic-Lacan M. Influence of hydroxypropyl-•-cyclodextrin complexation on piroxicam release from buccoadhesive tablets. Eur J Pharm Sci 2004; 21: 251-260.

Cómo citar
1.
YEDURKAR P, DHIMAN M, SAWANT K. Comprimidos mucoadherentes bicapa para la administración bucal de carvedilol: Estudios in vitro e in vivo. Ars Pharm [Internet]. 20 de septiembre de 2007 [citado 2 de diciembre de 2022];48(3):259-74. Disponible en: https://revistaseug.ugr.es/index.php/ars/article/view/4990

Descargas

La descarga de datos todavía no está disponible.