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. 2023 Oct 31;15(11):2558.
doi: 10.3390/pharmaceutics15112558.

Solubility and Physical Stability Enhancement of Loratadine by Preparation of Co-Amorphous Solid Dispersion with Chlorpheniramine and Polyvinylpyrrolidone

Krit Suknuntha  1   2 , Nattakanwadee Khumpirapang  3 , Vimon Tantishaiyakul  1   2 , Siriporn Okonogi  4   5
Affiliations

Solubility and Physical Stability Enhancement of Loratadine by Preparation of Co-Amorphous Solid Dispersion with Chlorpheniramine and Polyvinylpyrrolidone

Krit Suknuntha et al. Pharmaceutics. .

Abstract

Loratadine (LRD), a non-sedating and slow-acting antihistamine, is often given in combination with short-onset chlorpheniramine maleate (CPM) to increase efficacy. However, LRD has poor water solubility resulting in low bioavailability. The aim of this study was to improve LRD solubility by preparing co-amorphous LRD-CPM. However, the obtained co-amorphous LRD-CPM recrystallized rapidly, and the solubility of LRD returned to a poor state again. Therefore, co-amorphous LRD-CPM solid dispersions using polyvinylpyrrolidone (PVP) as a carrier were prepared. The obtained solid dispersions were characterized using X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR). The solubility, dissolution, and mechanism of drug release from the LRD-CPM/PVP co-amorphous solid dispersions were studied and compared with those of intact LRD, LRD/PVP solid dispersions, and co-amorphous LRD-CPM mixtures. The results from XRPD and DSC confirmed the amorphous form of LRD in the co-amorphous solid dispersions. The FTIR results indicated that there was no intermolecular interaction between LRD, CPM, and PVP. In conclusion, the obtained LRD-CPM/PVP co-amorphous solid dispersions can successfully increase the water solubility and dissolution of LRD and extend the amorphous state of LRD without recrystallization.

Keywords: amorphous; chlorpheniramine; film casting; loratadine; polyvinylpyrrolidone; quench cooling; solid dispersion; solubility enhancement.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structure of LRD (A), CPM (B), and PVP (C).
Figure 2
Figure 2
DSC thermograms of the amorphous LRD and co-amorphous LRD-CPM solid dispersions in comparison with the intact drugs and PVP.
Figure 3
Figure 3
XRPD patterns of the amorphous LRD and co-amorphous LRD-CPM solid dispersions in comparison with the intact drugs and co-amorphous mixture of LRD-CPM (am) after being freshly prepared (A) and kept for 30 days (B).
Figure 4
Figure 4
XRPD patterns of the co-amorphous mixture of LRD-CPM (am) after storage for 30 days in comparison with the intact polymorphic forms of LRD.
Figure 5
Figure 5
XRPD patterns of the amorphous LRD and co-amorphous LRD-CPM solid dispersions at 90 days (A), 180 days (B), and 360 days (C) of storage.
Figure 6
Figure 6
FT-IR spectra patterns of the co-amorphous LRD-CPM solid dispersions, CPM/PVP and LRD/PVP solid dispersions, and co-amorphous LRD-CPM mixture in comparison with the intact drugs and PVP (A) and wavenumber amplification in 1900–1300 cm−1 range of LRD/PVP solid dispersion (B), CPM/PVP solid dispersion (C), co-amorphous LRD-CPM mixture (D), and co-amorphous LRD-CPM/PVP solid dispersions (E).
Figure 7
Figure 7
Dissolution profiles of LRD/PVP solid dispersions (A) and co-amorphous LRD-CPM/PVP solid dispersions (B) in comparison with intact LRD, co-amorphous LRD-CPM mixture, and LRD-CPM physical mixture in simulated intestinal fluid pH 6.8.
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