News from Europe's pharmaceutical manufacturing industry coupled with upcoming events, and exclusive articles and interviews from industry experts. WEEKLY
Formulation and Evaluation of an Effervescent, Gastroretentive Drug-Delivery System
The authors developed a formulation for effervescent gastroretentive drug delivery techniques using ibuprofen as a model drug. They optimized the formulations by applying full factorial design.
Formulation optimization. Experimental design can be defined as the strategy for setting up experiments in such a manner that the required information
is obtained as efficiently and precisely as possible. The development of a new pharmaceutical formulation usually entails
optimization. Factorial design is a system of experimental design by which the factors involved in a reaction or a process
can be identified and their relative importance assessed. Factorial design has the following advantages (10, 11):
It can be the design of choice for examining treatment variations because it has great flexibility for exploring or enhancing
the signal (i.e., treatment) in studies.
It is efficient because instead of conducting a series of independent studies, one can combine the studies into one.
Factorial designs are the only effective way to examine interaction effects. They allow scientists to separate the important
factors from the unimportant factors. In factorial designs, a factor is a major independent variable. A level is a subdivision
of a factor.
Table II: 23 two-level, full factorial design (factors X1, X2, and X3).
Formulation trials. For the present study, 23 full factorial designs were selected. A polymer's viscosity grade is an important consideration in tablet formulation (12).
When developing a controlled-release system that releases gas after contact with gastric fluid, a disintegrating agent also
is important because it ensures that the swollen matrix disintegrates slowly (13, 14). So the ratios of HPMC K4M to HPMC K15M
(2:1 and 1:1), the amounts of Carbopol (0 and 30 mg), and the amounts of sodium bicarbonate (90 and 144mg) were chosen as
independent variables and studied at two levels of C1 (min) and C2 (max). Because the batches were optimized by 23 factorial designs, eight experiments were performed (see Table II). Total weight of the tablets was kept 700 mg by taking
310 mg (approx 45%) of drug mixed with excipients. Lactose was added to make up the total theoretical weight of the tablets.
The ingredients were weighed accurately and mixed thoroughly. Effervescent controlled-matrix tablets were manufactured by
direct compression of formulation ingredients with a sixteen-punch rotary tablet press (Pharmac, Pharmaceutical Machine Works,
Indore, India). Magnesium stearate was used as a lubricant. Eight formulations were prepared and coded from F1 to F8. Each
formulation's composition is summarized in Table III. Dissolution tests were performed using US Pharmacopeia Apparatus 2, at pH 1.2 to mimic the conditions that exist in the gastrointestinal tract (15).
Table III: Various batch formulations.
Optimization of tablet batches on the basis of floating behavior. The randomly selected tablets from each formulation were kept in a 100-mL beaker containing simulated gastric fluid, pH 1.2
as per USP. The time taken for the tablet to rise to the surface and float was considered the floating lag time (FLT). The length of
time that the dosage form remained on the surface of the medium was considered the total floating time (TFT) (16). Formulations
F1, F2, F3, and F5 started to float after 5 min. Formulations F1, F2, F4, and F6 were dissolved within 3 h. Formulations F7
and F8 started to float within 1 min and swelled. Only formulation F8 maintained its integrity and floated for more than 24
h. Floating behavior is summarized in Table IV. Formulation F8 was selected as the optimized formulation because of its floating
behavior.
Table IV: Floating behavior of various formulations.
Physical evaluation of the optimized tablet formulation. The optimized tablet formulation's organoleptic properties were evaluated, and thickness and diameter were measured using
vernier calipers (17). A weight-uniformity test was conducted on 20 of the prepared floating tablets. Tablet hardness was
evaluated with a Monsanto tester (THT, Industrial Pharma, Delhi, India). The authors used a Roche type friabilator (EF-2,
Electrolab, Delhi, India) to gauge the friability of 10 tablets (17, 18). All evaluated test data of the optimized tablet
formulation were within pharmacopeial limits.
