Evaluation of Ampicillin- Lactose Incompatibility Reactions at Solid-State Using Physicochemical Methods

Background & Aims: One of the significant steps in the preformulation of pharmaceutical dosage forms is to examine active
pharmaceutical ingredient (API) compatibility with the excipients applied with it. Drug-excipient incompatibility affects the stability,
effectiveness, safety, and quality of the final product. Therefore, it is vital, for fruitful drug production, to sort out excipients compatible
with the active pharmaceutical ingredient. The aim of this study was to evaluate the compatibility of ampicillin with lactose through
differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) physicochemical methods.
Materials & Methods: To formulate powder samples, 300 mg ampicillin and lactose powder was discharged into a vial in a ratio of 1:
1, and 20% v/w water was added and then vortexed. Also, samples of pure drug and pure excipient were prepared by the same method.
The direct compression method was applied to formulate the tablet samples. The samples were stored at 60° C in the oven and possible
incompatibilities were examined for four consecutive weeks by observing the DSC thermograms and FTIR spectra.
Results: According to the results, it is recommended to eschew the formulation of ampicillin with lactose for possible incompatibilities.
Conclusion: Based on the obtained results and the changes in the main peaks of absorption of the drug-excipient mixture in the fourth
week compared to the first day, there is the possibility of incompatibility in the mixture of ampicillin and lactose. Also, the observation
of discoloration in the powder and tablets in the fourth week compared to the first day indicates the occurrence of a kind of
incompatibility in the drug-excipient mixture.