Health and service :: pharmaceutical production

Table 1. Formulation details and composition of the medium of two suspensions.  Materials Uses Amount in suspensions Suspension I Suspension II Simple syrup, NF Sweetening agent 1 Part 2 Parts Sorbitol syrup 70% Sweetening agent 1 Part 2 Parts Deionized distilled water Vehicle 3 Parts 1 part Tragacanth Suspending agent, Thickening agent 0.6% 0.6% Tween 80 Nonionic moisturizing agent 0.02% 0.02% Methyl paraben Preservative 0.1% 0.1% Propyl paraben Preservative 0.1% 0.1%    measuring tube No.2.   Sedimentation volume  The sedimentation volume (F) was obtained based on the following equation:  01VVF,   V1 is the equilibrium volume of sediment and V0 is the total volume of suspension before sedimentation. Equilibrium volume of sediment is the volume which remains unchanged for 3 weeks (Gennaro, 2000; Sinko, 2006).   Degree of flocculation  Degree of flocculation () was estimated using this equation:  FF,   F is the sedimentation volume of the flocculated suspension, and F is the sedimentation volume of the suspension when deflocculated (Gennaro, 2000; Sinko, 2006).  Ease of redispersibility: The number of shears required to redisperse a sedimented suspension in a cylindrical glass graduate is an indicator of ease of redispersibility (N) (Jones et al., 1970).   Freeze/Thaw cycles  Physical and microscopic changes of suspensions under sudden thermal changes were investigated. Suspensions were kept in a 40°C oven for 24 h and then transferred to a 0°C freezer for 24 h (Lieberman, 1990).   Normal temperature fluctuation  Inspection of physical and microscopic changes of the suspension during a gradual decrease in temperature from 40 to -5°C was also performed. For this purpose, suspensions were kept for 24 h in each temperature (Sinko, 2006).  pH of suspensions: pH of suspensions was determined using a Rotring pH meter (Dalal and Narurkar, 1991). Drug release studies  The USP paddle method was used for testing the release of theophylline from microcapsules and suspensions. Experiments were performed according to dissolution test No. II for sustained-release theophylline preparation using a USP dissolution apparatus (Pharma test, PTZWS3, Germany).   The dissolution medium was consisted of 900 ml phosphate buffer (pH 4.5) maintained at 37C stirred at rate of 75 rpm. An amount of microcapsule or suspension containing 100 mg theophylline was used for each dissolution experiment. At appropriate time intervals, 20, 40, 60, 90, 120, 180, 240, 300, 360, 420 and 480 min, a 3 ml sample of dissolution medium was withdrawn and replaced by an equal volume of medium to maintain the volume constant. Samples were filtered, diluted, and analyzed for theophylline concentration at 270 nm to characterize the dissolution profiles. For reading the absorbance of samples obtained from the dissolution of suspensions, dissolution media containing drug free suspension was used as the blank. Dissolution efficiency percentage after 8 h (DE8%) was considered as a basis for comparing the dissolution profiles. DE% was calculated based on the following equation:  100.%1000tydtyDEt  DE is the ratio of area under the dissolution curve at a given time to the total area at the same time once the entire content is released (Khan, 1975).   Kinetic models analysis  The release data were fitted to different kinetic models in Microsoft Excel 2007 software as follows to determine the model which better described the kinetics of the release behavior: First-order kinetic tkWW10lnln, Hixson-Crowell’s cube root of time tkWW23/103/1, and square-root of time 2/10ktWW, where W is the amount of drug remaining to be released and W0 is the initial amount of drug (Sprockel and Price, 1989).   Statistical analysis  SPSS software version 12 was used for all statistical analysis. Student t-test and one-way analysis of variance (ANOVA) followed by a Duncan post hoc test, was used for comparison between DE%