Abstract
INTRODUCTION.
Lack of national requirements regulating the quality of valacyclovir hydrochloride active pharmaceutical ingredient (API) in hydrated form and valacyclovir medicinal products may be challenging not only for manufacturers, but also for experts examining submitted materials in registration dossiers. In this regard, it seems relevant to analyze the pharmacopoeial requirements for the quality of the pharmaceutical substance valacyclovir hydrochloride and medicinal products containing valacyclovir for applicants preparing the registration dossier and for experts examining the quality of medicinal products.
AIM.
This study aimed to analyze and generalize quality requirements for valacyclovir medicinal products: pharmaceutical substance in anhydrous and hydrated form and tablets.
MATERIALS AND METHODS.
The study compared quality requirements for valacyclovir hydrochloride API described in the State Pharmacopoeia of the Russian Federation, Edition XV (SP RF), European (Ph. Eur.), British (ВР), US (USP), Indian (IP), Chinese (ChP), and Japanese Pharmacopoeias (JP), as well as registration dossiers of valacyclovir hydrochloride tablets described in BP, USP, IP, ChP, and JP monographs.
RESULTS.
Valacyclovir hydrochloride is a medicinal product used to treat herpesvirus infections. Russian State Register of Medicines includes APIs from 6 manufacturers and 17 products in the dosage form of film-coated tablets (of them 14 registered in the Eurasian Economic Union). A pharmacopoeial monograph on valacyclovir hydrochloride API is included in the SP RF, Ph. Eur., BP, USP, IP, ChP, and JP. Ph. Eur., BP, USP, and IP establish requirements for both anhydrous and hydrated forms of valacyclovir. In Ph. Eur. (BP), the impurity profile of anhydrous and hydrated forms of valacyclovir differs significantly, while other pharmacopoeias have different standards of water content. Valacyclovir tablets are described in BP, USP, IP, ChP, and JP. For this dosage form, either IR spectrometry method or both HPLC and UV spectrophotometry methods should be used for identification; it is recommended to specify the identified acyclovir impurity, unspecified impurities and a sum of impurities (organic impurities). Despite varying impurity profiles for hydrated API and anhydrous tablets, BP requirements are identical, no matter what substance is used.
CONCLUSIONS.
Comparative analysis of national pharmacopoeias and registration dossiers allows us to summarize the requirements for impurity control in valacyclovir API and tablets with different synthesis methods. Alternative methods have been found for identifying the API in valacyclovir products. A comparative analysis reveals differences in dissolution test standards across pharmacopoeias. Manufacturers can apply this point in the specifications, since this test confirms stability of the manufacturing process, batch homogeneity, and drug quality, rather than its comparability with comparator drugs.