Title : Nanoparticle Engineering of atovaquone using nano-by-design (NbD) approach
Abstract:
One of the major problems of poorly soluble drugs is low bioavailability. The problem is basically related with BCS class II drugs which are poorly soluble in both aqueous and nonaqueous media. Atovaquone (ATQ), a BCS class II molecule is primarily used to treat or prevent pneumonia caused by a fungal infection called Pneumocystitiscarinii (also called Pneumocystis jiroveci). Atovaquone (ATQ) is a highly lipophilic molecule (log P = 5.31) and practically insoluble in 0.1 N HCl and water. Further, it has a pKa of 9.1, rendering it essentially neutral under the pH of physiological conditions. This has resulted in its poor and unreliable absorption. Mean absolute bioavailability of ATQ is 21%. The aim of the present study was the development of nanosuspension of ATQ using Nano by design (NbD) approach to overcome bioavailability related issues associated with the drug. Microfluidization and High-pressure homogenization (HPH) techniques were used for the processing the formulation. The patient-centric quality target product profile (QTPP) and critical quality attributes (CQAs) were earmarked. Critical formulation parameters (CFPs) such as drug: stabilizer ratio and critical process parameters (CPPs) like number of cycles and pressure were identified as high impact parameters affecting particle size and polydispersibility index in risk assessment studies in both the techniques. A Box Benhken design (BBD) was employed for optimization. The design spaces were generated, and the optimum formulations were located using desirability parameters, followed by its validation. Further, the prepared nanosuspensions were characterized for the DSC, FTIR, XRD, In-vitro dissolution studies etc. The results were compared to pinpoint merits and demerits of both the techniques.
Takeaway Notes:
•The audience will learn two techniques of nanoformulations viz. high pressure homogenization and microfluidic homogenization as well as the regulatory perspective of using Nano-by-design approach.
•Other faculty could use the technology for BCS class II and IV drugs.
•The technology could be used to decrease the dose and dosage frequency of the developed dosage form.
