Abstract:
According to the biopharmaceutical classification system, Clarithromycin is
considered a class II molecule with low solubility. Poorly soluble drugs result in low
bioavailability. Various techniques have been studied to improve the solubility of
drugs and subsequently bioavailability. Of these techniques, preparation of
amorphous form is the preferred method because it is a more effortless and
convenient way to improve the aqueous solubility and dissolution of poorly water soluble drugs. The only disadvantage of amorphous materials is that they are less
thermodynamically stable and can recrystallize during processing and storage.
Aim:
The aim of this study is to prepare amorphous form of clarithromycin to improve its
solubility, dissolution rate, and, subsequently, bioavailability.
Methods:
In this study, preparation of amorphous form of clarithromycin was conducted using
the quench cooling method in which the purchased anhydrous crystalline
clarithromycin was spread on an aluminum foil and heated to a melting point (217˚C
- 220˚C) and then rapidly cooled. Various techniques were conducted to
characterize the prepared amorphous clarithromycin, and these include Differential
Scanning Calorimetry (DSC), Fourier-Transform Infrared Spectroscopy (FTIR), and
X-Ray Powder Diffraction (XRPD). In addition, tablets were formulated using the
amorphous clarithromycin mixed with selected excipients from compatibility studies,
and in vitro dissolution and stability studies were conducted over a period of 6
months.
Results:
The DSC thermogram results confirmed that the material prepared using the
quench cooling process is an amorphous solid-state. Furthermore, the XRPD
confirmed an amorphous solid-state with scattering halo peaks. The FTIR also
depicted some broader and lower intensity peaks that indicated a formation of an
amorphous material. The dissolution rate of amorphous clarithromycin tablets
improved by more than 30% when compared to commercial crystalline
clarithromycin tablets. The study revealed a drop in dissolution rate at months 3 to
6 under accelerated conditions due to recrystallization. The 6 monthly stability study
at long term conditions showed no change in the integrity of the tablets and their
contents.
Conclusion:
As indicated by the study, it can be concluded that the amorphous clarithromycin
remained stable during processing and storage under long-term stability for 6
months. Furthermore, based on dissolution results, it can be concluded that
amorphous solids have an improved dissolution rate.
