Development of an Osmotically Controlled Drug-Delivery System of Glipizide - Pharmaceutical Technology

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Development of an Osmotically Controlled Drug-Delivery System of Glipizide
The authors describe the development of an inclusion complex of GLZ and formulated an extended-release dosage form based on osmotic technology.


Pharmaceutical Technology
pp. 80-91

Formulation development of an EOPT. The dosage form was designed as a tablet core coated with a semipermeable membrane that had a preformed passageway. The core tablets consisted of a GLZ complex along with osmagent and other conventional excipients. The core compartment was surrounded by a semipermeable membrane. After administration, the core compartment absorbs aqueous fluids from the surrounding environment through the membrane. After coming into contact with the aqueous fluids, the GLZ complex dissolves, and the dissolved drug is released through the drilled orifice.

Core tablets were evaluated for various pharmacotechnical parameters. The tablets' hardness was in the range of 4.0–6.0 kg/cm2 . The percentage friability of all formulations was below 1%, which was within the prescribed limits. Friability directly affects tablet. In a weight-variation test, the pharmacopoeial limit for the percentage deviation of all the tablets was less than 7.5%. The tablets contained 97–102% of the labeled amount of GLZ, thus indicating drug-content uniformity.


Figure 7: In vitro drug-release profile of the elementary osmotic-pump tablet.
Figure 7 shows that variations in the formulation of the core tablet had a marked influence on GLZ release. Variation in the amount of osmotic promoting agent and swelling polymer influenced the drug-release rate and the amount of drug released in 24 h. Tablets' release rate and cumulative release at 24 h were higher in formulations that included NaCl than in those that included KCl. Tablets that included HPMC K4M had a lower drug release rate than those that included NaCl and KCl. The release rate increased as the amount of NaCl or KCl increased. The more NaCl or KCl was incorporated into a tablet, the more water was absorbed, the more the core formulation could be liquefied, and the more GLZ was released. HPMC K4M played the role of a thickening agent and elevated the viscosity of the tablet. As a consequence, less GLZ was released from the EOPT. Incorporating HPMC K4M with NaCl or KCl in a tablet formulation resulted in a lower drug-release rate, but produced a constant release rate over an extended period.


Figure 8: a) Membrane structure of batch B before dissolution studies, and b) membrane structure of batch B after dissolution studies.
SEM. To investigate the changes in the membrane structure, the authors studied the surface of the coated tablets using SEM. Figure 8 shows SEM micrographs of the membrane surface of batch B before and after dissolution studies were performed.

Figure 8a shows the membrane structure of batch B before dissolution studies were performed. The surface of the coated tablet was smooth before coming into contact with the aqueous environment, and the coats appeared to be free of defects. Figure 8b shows an SEM micrograph of an excised section of the top surface of the membrane after the dissolution study was performed. It exhibited a surface morphology similar to that in Figure 8a, suggesting that pores had not developed in the membrane or been affected by the in vitro drug-release profile.

Conclusion

The authors' experiment showed that the dissolution rate of GLZ increased when it was dispersed in HP–β–CD. The complex formation was confirmed by DSC and FTIR. The increased dissolution rate in systems containing HP–β–CD was likely the result of the increased wettability and dispersibility of GLZ. Examination of the EOPT indicated that the osmotic promoting agent and swelling polymer significantly affected the in vitro drug-release profile.

Ritesh B. Patel* is a lecturer, and Rakesh P. Patel is an associate professor, both at S.K. Patel College of Pharmaceutical Education and Research, Ganpat University, Ganpat Vidyanagar, Kherva, Mehsana-Gozaria Highway, PIN-382711, Gujarat, India,
. Madhabhai M. Patel is a principal of Kalol Institute of Pharmacy.

*To whom all correspondence should be addressed.

Submitted: Oct. 7, 2009. Accepted: Jan. 13, 2010.


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