Freeze Dried Quetiapine-Nicotinamide Binary Solid Dispersions: A New Strategy for Improving Physicochemical Properties and Ex Vivo Diffusion.

Ahmed Mahmoud Abdelhaleem Ali,Mayyas Mohammad Ahmad Al-Remawi

doi:10.1155/2016/2126056

Ahmed Mahmoud Abdelhaleem Ali, Mayyas Mohammad Ahmad Al-Remawi

Open Access

https://doi.org/10.1155/2016/2126056

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Abstract

Improving the physicochemical properties and oral bioavailability of quetiapine fumarate (QF) enabling enhanced antipsychotic attributes are the main aims of this research. The freeze dried solid dispersion strategy was adopted using nicotinamide (NIC) as highly soluble coformer. The prepared dispersions were characterized using scanning electron microscopy (SEM) differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Static disc intrinsic dissolution rate and ex vivo diffusion through intestinal tissues were conducted and compared to pure quetiapine fumarate. The results demonstrated a highly soluble coamorphous system formed between quetiapine fumarate and nicotinamide at 1 : 3 molar ratio through H-bonding interactions. The results showed >14-fold increase in solubility of QF from the prepared dispersions. Increased intrinsic dissolution rate (from 0.28 to 0.603 mg cm−2 min−1) and faster flux rate through duodenum (from 0.027 to 0.041 mg cm−2 h−1) and jejunum (0.027 to 0.036 mg cm−2 h−1) were obtained. The prepared coamorphous dispersion proved to be effective in improving the drug solubility and dissolution rate and ex vivo diffusion. Therefore, binary coamorphous dispersions could be a promising solution to modify the physicochemical properties, raise oral bioavailability, and change the biopharmaceutics classification (BCS) of some active pharmaceutical ingredients.

Highlights

Quetiapine fumarate (QF) is a dibenzothiazepine antipsychotic drug used in treatment of schizophrenia and mania associated with type intensity of the sample (Is) bipolar disorders [1]
Quetiapine pharmacokinetics may change when concomitantly administered with some drugs such as ketoconazole, phenytoin, or rifampicin which affect the activity of CYP3A4 enzymes [4]
The prepared dispersions showed lower melting temperatures compared to parent components as displayed in Table 2 containing the thermal data of QF/NIC coamorphous dispersions

Summary

Introduction

Quetiapine fumarate (QF) is a dibenzothiazepine antipsychotic drug used in treatment of schizophrenia and mania associated with type I bipolar disorders [1]. The high frequency of administration of quetiapine (2–4 times daily) often results in numerous side effects including panic attacks, dyspnea, and swelling of lips and face [2]. Quetiapine has high affinity to serotonin 5HT2 than dopamine receptors which makes it suitable for successful control of psychotic symptoms associated with Parkinson’s disease without worsening of body movements [5]. Quetiapine is soluble in acidic pH (2–4); due to its low water solubility over the physiological pH and high permeability, it was classified as BCS class II drug [6]. Solid state modification approaches which will increase its water solubility are expected to improve its bioavailability and enable bypassing hepatic metabolism if administered in suitable dosage form such as orodispersible or sublingual tablets or films. The increased solubility by new formulation will enable development of new and predictable

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Conclusion