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 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 7: In vitro drug-release profile of the elementary osmotic-pump tablet.
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 8: a) Membrane structure of batch B before dissolution studies, and b) membrane structure of batch B after dissolution
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.
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, firstname.lastname@example.org
. 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.