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A Dual Controlled Gastrointestinal Therapeutic System of Salmon Calcitonin. II. Screening of Process and Formulation Variables

An important aspect of the “Desired State” of manufacturablity as defined by the International Committee of Harmonization is the mechanistic understanding and predictability of dosage forms at the laboratory scale. The accomplishment of that aspect is often preceded by a formulation knowledge and previous history of the project or by screening of the variables to identify the critical ones. Osmotically controlled drug delivery systems provide a means of eliminating the effect of pH, food as well as transit time on drug release. Salmon calcitonin, a hypocalcemic peptide, was formulated as an osmotically controlled bilayered enteric‐coated dosage form with turkey ovomucoid (enzyme inhibitor) and glycyrrhetinic acid (permeation enhancer) along with other excipients. Drug release from the dosage form is generally affected by formulation and process variables. However, the literature information is very limited for the effects of these variables on the release kinetics of peptide drugs from osmotically controlled systems. The objective of this study was to evaluate the factors that influence the release of the drug from bilayered, osmotically controlled tablets coated with a semipermeable membrane of cellulose acetate. A seven‐factor‐12‐run Plackett‐Burman screening technique was employed to evaluate the effects of orifice size, coating level, amounts of sodium chloride, Polyox® N10 and N80 and Carbopol® 934P and 974P on drug release. Response variables was cumulative percent released in 24 hr with constraints on time for 25% and 50% drug release. Factors showing maximum influence on drug release were amounts of Carbopol® 934P and Polyox® N10 in the drug layer, orifice size and coating level showing negative effects with the main effect magnitudes of − 30.85, − 10.97, − 9.61, and − 9.95, respectively.