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Preparation and in vitro-in vivo evaluation of double layer coated and matrix sustained release pellet formulations of diclofenac potassium.
Int J Pharm. 2011 Mar 15; 406(1-2):84-90.IJ

Abstract

The purpose of the present study was to prepare matrix extended release pellets of diclofenac potassium using low amount of release-modifying agents and, to compare its performance in vivo with coated pellets and matrix tablets. Coated pellets were prepared by extrusion-spheronization, followed by double layer coating using different polymers separately. Matrix pellets with different release rate in vitro were prepared by extrusion-spheronization with different kinds of retarding materials. Bioavailability study of different coated pellets revealed that the drug concentration in plasma of beagle dogs was too low to be detected and, implied that the drug was nearly not released from the preparations before reaching colon due to the appearance of lag time in the dissolution process. The phenomenon indicated that slow-release pellets of diclofenac potassium perhaps should not be developed as double membrane-controlled type. The AUC((0 → 24)) of the immediate release pellets, the two matrix pellets and the reference were 304.4, 87.7, 204.1 and 179.1 μg h/ml, respectively. The C(max) of the formulations mentioned above were 46.3, 13.0, 33.6 and 32.1 μg/ml, respectively. All the matrix formulations, including the reference, exhibited incomplete absorption due to the short small intestine transit time and termination of the drug release in the colon because of its limited solubility. The matrix pellets were bioequivalent with the commercially available tablet (Voltaren(®)) although the drug release in vitro of the former was much faster, while the bioavailability of the matrix pellets with similar in vitro drug release to the reference (Voltaren(®)) was much lower than the latter. The results perhaps was caused by lacking of physical robustness in the waxy tablet formulation, resulted in low wet strength and easily destroyed by the mechanical destructive forces and finally introduced faster drug release rate in vivo. It is apparent that preparations with similar performance in vitro may differ a lot in vivo because of the differences in drug release rate in vivo owing to various wet strengths of excipients contained, especially for sustained release products.

Authors+Show Affiliations

Department of Pharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, Liaoning, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21219996

Citation

Fu, Jijun, et al. "Preparation and in Vitro-in Vivo Evaluation of Double Layer Coated and Matrix Sustained Release Pellet Formulations of Diclofenac Potassium." International Journal of Pharmaceutics, vol. 406, no. 1-2, 2011, pp. 84-90.
Fu J, Wang X, Xu L, et al. Preparation and in vitro-in vivo evaluation of double layer coated and matrix sustained release pellet formulations of diclofenac potassium. Int J Pharm. 2011;406(1-2):84-90.
Fu, J., Wang, X., Xu, L., Meng, J., Weng, Y., Li, G., He, H., & Tang, X. (2011). Preparation and in vitro-in vivo evaluation of double layer coated and matrix sustained release pellet formulations of diclofenac potassium. International Journal of Pharmaceutics, 406(1-2), 84-90. https://doi.org/10.1016/j.ijpharm.2010.12.043
Fu J, et al. Preparation and in Vitro-in Vivo Evaluation of Double Layer Coated and Matrix Sustained Release Pellet Formulations of Diclofenac Potassium. Int J Pharm. 2011 Mar 15;406(1-2):84-90. PubMed PMID: 21219996.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Preparation and in vitro-in vivo evaluation of double layer coated and matrix sustained release pellet formulations of diclofenac potassium. AU - Fu,Jijun, AU - Wang,Xiaoli, AU - Xu,Lishuang, AU - Meng,Jia, AU - Weng,Yan, AU - Li,Guofei, AU - He,Haibing, AU - Tang,Xing, Y1 - 2011/01/08/ PY - 2010/11/09/received PY - 2010/11/30/revised PY - 2010/12/29/accepted PY - 2011/1/12/entrez PY - 2011/1/12/pubmed PY - 2011/6/4/medline SP - 84 EP - 90 JF - International journal of pharmaceutics JO - Int J Pharm VL - 406 IS - 1-2 N2 - The purpose of the present study was to prepare matrix extended release pellets of diclofenac potassium using low amount of release-modifying agents and, to compare its performance in vivo with coated pellets and matrix tablets. Coated pellets were prepared by extrusion-spheronization, followed by double layer coating using different polymers separately. Matrix pellets with different release rate in vitro were prepared by extrusion-spheronization with different kinds of retarding materials. Bioavailability study of different coated pellets revealed that the drug concentration in plasma of beagle dogs was too low to be detected and, implied that the drug was nearly not released from the preparations before reaching colon due to the appearance of lag time in the dissolution process. The phenomenon indicated that slow-release pellets of diclofenac potassium perhaps should not be developed as double membrane-controlled type. The AUC((0 → 24)) of the immediate release pellets, the two matrix pellets and the reference were 304.4, 87.7, 204.1 and 179.1 μg h/ml, respectively. The C(max) of the formulations mentioned above were 46.3, 13.0, 33.6 and 32.1 μg/ml, respectively. All the matrix formulations, including the reference, exhibited incomplete absorption due to the short small intestine transit time and termination of the drug release in the colon because of its limited solubility. The matrix pellets were bioequivalent with the commercially available tablet (Voltaren(®)) although the drug release in vitro of the former was much faster, while the bioavailability of the matrix pellets with similar in vitro drug release to the reference (Voltaren(®)) was much lower than the latter. The results perhaps was caused by lacking of physical robustness in the waxy tablet formulation, resulted in low wet strength and easily destroyed by the mechanical destructive forces and finally introduced faster drug release rate in vivo. It is apparent that preparations with similar performance in vitro may differ a lot in vivo because of the differences in drug release rate in vivo owing to various wet strengths of excipients contained, especially for sustained release products. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/21219996/Preparation_and_in_vitro_in_vivo_evaluation_of_double_layer_coated_and_matrix_sustained_release_pellet_formulations_of_diclofenac_potassium_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(11)00018-4 DB - PRIME DP - Unbound Medicine ER -