Abstract

With the advancement in the manufacturing industry of the food additive and supplements coupled with ever increasing challenges in the health risk hazards, establishment of strict control measures become essential to ensure product quality and safety. A small firm for manufacturing of food supplements and additives established production line for new product based on L-ascorbic acid (vitamin C) 500mg per hard gelatine capsule. Ascorbic Acid is provided as sustained release pellets. One of the important quality control tests that should be inspected were the dissolution profile after one, four and eight hours. Dissolution rate test was performed for 70 consecutive batches and results were interpreted. The best fitting model that described the dissolution rate was Morgan-Mercer-Flodin (MMF) Model which is Sigmoidal four parameter mathematical curve. Establishment of Control Limits (CLs) was determined for each chronological test point using commercial statistical software package. Control limits standard deviations (sd) for one, four and eight hours were 28.1%±3.5%, 68.1%±4.1% and 89.4%±3.3%, respectively. On the other hand, the calculated lower and upper control limits (LCL, UCL) were (21.1%, 35.1%), (59.3%, 77.0%) and (81.6%, 97.2%), respectively. Interestingly, no Out-Of-Specification (OOS) results were detected for individual lots of product, yet UCLs exceeded Upper Specification Limits (USLs). This shift in the dissolution rate process is evident especially in four hours point. Within/Overall Capability plots confirmed this finding with strong shift was detected to the right side that indicated crucial need for investigational analysis. Accordingly, Statistical Process Control (SPC) provided provision for early warning of deviations in the manufacturing process cycle of the product before any true excursions may occur. The selection of product that has simple manufacturing processing steps such as Vitamin C will aid in the spotting of the most probable causes of hidden deviations which may be related to consistency of raw materials quality and/or laboratory system related-deviations.

Keywords: Ascorbic acid; Hard gelatin capsule; Pellets; Dissolution rate; MMF model

Abbreviations: MMF: Morgan Mercer Flodin; CL: Control Limit; LCL: Lower Control Limit; UCL: Upper Control Limit; USL: Upper Specification Limit; SPC: Statistical Process Control; HGC: Hard Gelatin Capsule; API: Active Pharmaceutical Ingredient; QC: Quality Control; QA: Quality Assurance