Pharmaceutical Quality Management
Materials- All the chemicals employed were procured from the indigenous manufacturers
and were use without further purification. Gelatin (type A, Protein products of India), copper sulphate pentahydrate, zinc sulphate heptahydrate, magnesium oxide, potassium iodide, managanese sulphate tetra hydrate and ferrous sulphate heptahydrate were of analytical grade (Qualigens). Other materials used included, dicalcium phosphates anhydrous USP (Enar chemie), red oxide of iron [RO] (SD chemicals), ferrous fumarate IP
(Bakul products), sodium methyl and propyl p-amino benzoates IP (Ben Chem), calcium chloride dihydrate (E.Merck), enzyme alcalase (Novo industry A/S, Denmark), glycerine IP (Godreig soaps), hydrochloric acid (Qualigens) and demineralised water.
Characterization of gelatin- Gelatin was characterized by determination of-
(i) Isoelectric point – IEP-
The IEP of gelatin was determined using 30 g of 1 % w/w gelatin solution (prepared in demineralized water) and measuring its zeta potential before and after addition of one drop of 0.1 N HCl. The IEP was found to be 4.85
(ii) Bloom strength- and
(iii) Viscosity of the gel.
The bloom strength (using previously calibrated Boucher electronic jelly tester) and viscosity (using Oswald viscometer BSS-C) were determined on 6.67 % w/w gel. The bloom strength was found to be 192.5 bloom grams and the viscosity value was 0.0304 poise.The results indicated that gelatin used was of Type A.
Solid phase interactions-
In the preliminary studies, interactions between gelatin and minerals was investigated using different techniques. Based on these results, formulation studies were carried out employing only those combinations, which showed probable interactions.
Formulation studies- study design
A low (-) and high (+) value of each salt (except DCP, zinc sulphate and magnesium oxide which were eliminated on the basis of preliminary data) was selected depending on the concentrations of these salts occurring in commercial brads of hematinic soft gelatin –mineral capsules. Copper sulphate (+/-:30.0 mg/ 3.0 mg), potassium iodide (+/- : 2.5 mg /0.1 g) and manganese sulphate (+/-:2.5/0.5 mg) were suspended and along with RO/ FF (1 % w/w) in groundnut oil and later encapsulated in soft gelatin shells on a rotary die machine, Scherer model (Tool Tronics Ltd). About 5000 capsules were manufactured for the study.
The capsules were placed in stoppered amber colored glass bottles protected from light and stored under exaggerated conditions of temperature viz. 40 + 2 oC and 50 + 2 oC for 2 months. Control samples were maintained at refrigeration temperature (8 degC) for the same period rupture and dissolution time of both
fresh and stored capsules were evaluated in 600 ml of 0.1 N HCl (pH 1.6 + 0.2) using apparatus II in a 6- station USP XXII dissolution rate test apparatus. The medium was stirred at 100 rpm. The capsules were evaluated both for the shell rupture time and the dissolution time.
Few shells of the stored capsules were investigated for their ionic content using atomic absorption spectrophotometer (Perkin Elmer model 3100). Standard solutions of copper, potassium and manganese were made. A calibration curve was plotted for each metal ion employing following parameters viz. Cu+2 (30 mA,
λ=324.7nm), Mn+2 (4mA, λ = 278.9 nm) and K+1 (8mA, λ = 766.6 nm). The results were statistically analyzed using 3-point regression analysis.