Stability of polymorphic forms of ranitidine hydrochloride

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry

Background:

• Ranitidine hydrochloride (HCl) exhibits polymorphism, with distinct Form I and Form II.
• Understanding the stability of these polymorphic forms is crucial for pharmaceutical manufacturing and storage.

Purpose of the Study:

• To investigate the stability of ranitidine-HCl Form I under various powder pretreatments simulating manufacturing conditions.
• To assess the stability of ranitidine-HCl Form I and Form II mixtures under different storage conditions (temperature and humidity).

Main Methods:

• Characterization of ranitidine-HCl forms using X-ray powder diffraction (XRPD), hot stage microscopy (HSM), and differential scanning calorimetry (DSC).
• Development and application of a quantitative XRPD method to determine the ratio of Form II to Form I.
• Exposure of Form I to pretreatments (mixing, compression, grinding, solvent contact) and storage under controlled temperature (20-42°C) and relative humidity (45-75% RH) for 6 months.

Main Results:

• Ranitidine-HCl Form I remained stable through most pretreatments, including mixing with Form II or excipients, compression, grinding, and contact with isopropanol or water/isopropanol mixtures followed by drying.
• Drying after water addition to Form I powder resulted in a mixture of Form I and Form II.
• Storage in airtight containers at room temperature and low humidity did not alter the Form II:Form I ratio.
• High humidity storage (especially at 30°C/75% RH) led to a preferential loss of Form II.
• An acidic environment at 42°C/45% RH also caused preferential loss of Form II.

Conclusions:

• Ranitidine-HCl Form I demonstrates good stability against common manufacturing powder pretreatments.
• The polymorphic composition of ranitidine-HCl is sensitive to storage conditions, particularly high humidity and acidic environments, which can lead to the degradation of Form II.
• Careful control of humidity and pH during storage is essential to maintain the desired polymorphic form of ranitidine-HCl.