USP-simulated gastric fluid

Dissolution testing is carried out in United States Pharmacopeia (USP) Apparatus I (100 rpm) or Apparatus II (50 rpm) utilizing 900 ml of the following dissolution media (1) 0.1 N HC1 or simulated gastric fluid USP without enzymes (2) a pH 4.5 buffer and (3) a pH 6.8 buffer or simulated intestinal fluid USP without enzymes. When 85% of the labeled amount of... 

All chemicals were used as received. PDADMAC and PAMPS were obtained from Aldrich Chemical Co. (Milwaukee, WI). Diclofenac sodium, sodium sulfathiazole, labetalol HCl, propranolol HCl, verapamil HCl, and diltiazem HCl were purchased from Sigma Chemical (St. Louis, MO). Dextrose USP was obtained from Amend Co. (Irvinton, NJ). Water was distilled and deionized using a Nanopure purihcation system (Fischer Scientihc, Fair Lawn, NJ). Simulated intestinal fluid was prepared using a O.OIM phosphate buffer (sodium phosphate monobasic and potassium phosphate dibasic) at pH 7 and 5.5 with different amounts of NaCl to vary the ionic strength. Simulated gastric fluid (pH 1.5) was prepared with concentrated HCl with different amounts of NaCl to vary the ionic strength. 

The release tests were performed using the USP dissolution method (apparatus I) and utilized 1000 ml of pH 1.2 simulated gastric fluid (USP XXI) or pH 6.8 simulated intestinal fluid (USP XXI) without enzymes, equilibrated to 37°C and stirred with the basket rotating at 50 or 150 rev/ min. Drug concentrations were assayed by UV spectrophotometry at 255 nm. The experiments were continued until 100% dissolution was achieved. The release data were analysed to zero order, calculating the slope and intercept of the line. Each data point is the average of six individual determinations. In all cases the standard deviation was less than 9%. 

Media include acidic media (e.g., 0.1 N HCl) or simulated gastric fluid, USP without enzymes, pH 4.5 buffer and pH 6.8 buffer of simulated intestinal fluid, USP without enzymes (From FDA Draff Guidance, Jan, 1999.)... 

Dissolution testing of indapamide is accomplished using the rotating basket method (USP Method I) with 900 mL of simulated gastric fluid T.S. without enzymes heated to 37<>C as the dissolution medium and a basket rotation of 100 rpm. Samples are placed in the baskets and the baskets are then lowered into the dissolution medium with samples withdrawn at appropriate intervals. The samples are filtered through 0.45 pm Miilipore filters. The dissolution medium is assayed for indapamide against appropriate standards using an UV absorbance assay (23). 

Another flavor of solubility that is typically studied for salt screening is intrinsic solubility. This experiment typically utilizes a compress pellet of pure API in a rotating die. This die is then placed into a USP dissolution apparatus, and the amount of drug released into a relevant media, such as water, simulated gastric fluid (SGF), or simulated intestinal fluid (SIF) is studied with time. This experiment provides information about the dissolution rate that can be expected for the pure drug substance. 

Fig. 11.3 Drug release proffle of verapamil HCl (240mg) extended release matrix tablets in simulated gastric (0-2h) and intestinal fluid (2-8h) without enzymes (900mL), using USP apparatus II at SOrpm...

Hydrochloric acid (0.01 or 0.1 mol 1 ) is the preferred medium for drugs that are readily soluble at gastric pH. Aqueous buffer solutions are used when solubility, dissolution rate, or drug stability are pH dependant. The use of simulated gastrointestinal fluids (from the USP), with or without enzymes, may be justified in some circumstances. 

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