The pharmaceutical industry is fast revamping and modernizing itself to meet the regulatory set-up of the country. Even as the pharmaceutical companies are abiding by the regulatory guidelines stated under the Drug Act,it is essential on the part of the government to create a robust regulatory system to ensure the quality and safety of drugs. Regulatory authorities like FDA regulate almost every facet of prescription drugs, including testing, manufacturing, labelling, advertising, marketing, efficacy and safety.
In order to cater to the needs of the regulated markets and to address the safety and quality of of the drugs, the pharma industry has to adopt sophisticated instruments and techniques. One such tool is Refractometry technique. Refractometers normally determine the critical angle. One essential part is prism of known refractive index in contact with the liquid to be examined. USP General Subchapter <831> on Refractive Index states the standard temperature for pharmacopeial measurements is 25°C. Many of the refractive index specifications in the individual monographs call for determining the value at 20°C. The temperature should be carefully adjusted and maintained, since the refractive index varies with the temperature. To achieve the theoretical accuracy of ±0.0001 RI, it is necessary to calibrate the instrument against a NIST traceable standard and to check frequently the temperature control and cleanliness of the prism.
Refractometer manufacturers now-a-days offer electronic temperature control from both prism and presser surfaces. The requirements of an electronically temperature controlled refractometer operating close to ambient air temperature are very different from the temperature control requirements of a refractometer operating more than 10°C from ambient. The temperature of the sample cover is controlled at the same temperature as that of the prism and when lowered, is designed to provide a temperature controlled microenvironment that provides unrivalled temperature stability, fast measurement time and minimal evaporation. This design minimizes the inaccuracies created by temperature gradients across the sample as deep well prisms fight to control temperature from the prism surface while the air and upper part of the sample have widely divergent temperatures.
Moreover, a refractometer can only achieve real world accuracy if the prism is cleaned properly between samples. The flat open sample area has no corners to trap even sticky materials and is resistant to almost all solvents including Acetone, Toluene and similar organics.
Similarly refractometers are now-a-days designed to withstand abuse of highly acidic chemicals like HCl and other caustic compounds. For these applications, manufacturers offer an extended chemical resistance option where the sample dish and cover are made from Hastelloy. Hastelloy is suggested for hydrofluoric acid at all concentrations, HCl and similar acids at all concentrations, strong alkalis & strong oxidizing agents.
Enflurane, Sevoflurane and similar halogenated ethers are used extensively for the induction and maintenance of general anaesthesia. Pharma manufacturers must comply with specifications from the USP/EP or relevant pharmacopoeia's. Many of these pharmacopoeia require the measurement of refractive index of Sevoflurane at an RI of 1.2745 - 1.2760 at 20°C. In such case one needs an instrument with RI range starting from 1.26.
For large hospitals doing their own pharmaceutical compounding, ensuring that their Total Parenteral Nutrition formulae are accurate is critical. Some manufacturer’s of instrument specifically customize to meet USP<797> requirement.
Labs doing hundreds of toxicology samples per day prefer to eliminate the human factor and choose large -scale automation. There are also modern day systems which combines a Refract system with a custom automation solution that minimizes sample use and replaces the tested sample to the testing vial.
The present day systems are user-friendly and produce better results. The features include Touch Screen with spill protection, memory cards for data storage & instrument-level 21 CFR part 11 compliant etc.
The author is associated with Agaram Industries, Hyderabad and can be
contacted at umesh@agaramindia.com