The influence of additives on the in vitro release of drugs from hard gelatin capsules

Abstract

A factorially designed experiment has been used to assess the total percentage of drug released from hard gelatin capsules in vitro as a function of (a) the drug—the drugs being nitrofurantoin, nitrofurazone, oxytetracycline dihydrate and tetracycline hydrochloride; (b) the diluent—the diluents being lactose, Primojel and Dry-Flow starch; (c) the quantity of diluent, either 20 or 80%; (d) the presence (at a 1 % level) and absence of magnesium stearate and (e) the presence (at a 1 % level) and absence of sodium lauryl sulphate. Treatment of the results by analysis of variance, in 5,4, 3 and 2 factor combinations, indicates that the influence of a given factor is often dependent on the other factors. These interdependencies take the form of either a variation in the extent of an effect or the reversal of an effect. The influence of drug and level of diluent show interdependencies of the former kind. Hence, whilst the overall average for drug release indicates that the drugs can be ranked in the ascending order: nitrofurantoin < nitrofurazone < oxytetracycline < tetracycline, the interactions predict that the quantitative ratios of 1:1·8:2·7:5·1 for the drugs above will vary when an additive is present and according to the additive. The rank order will, however, remain unchanged. Similarly, the higher level of diluent will usually increase drug release but not by a constant ratio between drugs. A reversal of an effect is shown by the addition of magnesium stearate, which in some instances increases rather than decreases drug release (its more usual effect). The addition of 1 % sodium lauryl sulphate does not provide a major enhancement of drug release, and in certain cases can be detrimental. There is no consistent order of effectiveness of the three diluents, and thus a universal capsule diluent, which will always improve drug release, does not appear to be a possibility.