Tramadol Hydrochloride: Study of the Production Process and Equipment Selection

Abstract

Tramadol is an Active Pharmaceutical Ingredient (API) found in various pharmaceutical formulations, designed to treat moderate to severe pain. The objective of this project is to study and determine the production process of tramadol through literature research on existing patents and ensuring adherence with Good Manufacturing Practices (GMP) regulations. The production process has been determined by studying equipment occupation times, and batch and cycle times. Initially, this study involves conducting a market analysis to determine the desired production quantity based on the product's characteristics and properties. It has been established that the annual production of tramadol will be 20 tons, meeting 10 % of the European demand. Assuming the plant operates for approximately 40 weeks per year, a batch size of 500 kg has been defined. The focus of the process is on the purification stage of tramadol, considering it is cheaper to purchase the isomeric mixture of the product as a raw material. For the discontinuous operation process, four vessels and two filters are required, including a bag filter and a Nutsche filter. The selected vessels have different characteristics depending on their task, capable of performing chemical reactions, crystallizations and/or mixtures. The filters, on the other hand, have been chosen accordingly. The Nutsche filter is used in two stages of the process, although only one has been found necessary for reasons of process optimization. An analysis of the operation times for each equipment has been conducted, allowing the determination of Key Performance Indicators (KPIs). By studying the operation times, the batch time of 51 hours and 30 minutes and the cycle time of 34 hours and 45 minutes have been determined. An analysis has been performed for production in campaigns, considering overlapping, and diverse campaign production options have been proposed for a year. In terms of KPIs, the maximum production capacity of tramadol per year and the minimum production time for the estimated quantity of 20,000 kg/year have been calculated. The maximum productioncapacity for the plant is 129 batches/year, equivalent to 64,500 kg of tramadol/year. The minimum production time is 1,406 hours and 45 minutes, which correspond to 58.61 days.