Understanding the Impact of Multi-factorial Composition on Efficient Loading of the Stable Ketoprofen Nanoparticles on Orodispersible Films Using Box-Behnken Design

Harsh G Shah; Vishal Rathod; Pratap Basim; Bhavin Gajera; Rutesh H Dave

doi:10.1016/j.xphs.2021.10.016

Understanding the Impact of Multi-factorial Composition on Efficient Loading of the Stable Ketoprofen Nanoparticles on Orodispersible Films Using Box-Behnken Design

J Pharm Sci. 2022 May;111(5):1451-1462. doi: 10.1016/j.xphs.2021.10.016. Epub 2021 Oct 20.

Authors

Harsh G Shah¹, Vishal Rathod¹, Pratap Basim², Bhavin Gajera³, Rutesh H Dave⁴

Affiliations

¹ Department of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, USA.
² Department of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, USA; Thermo Fisher Scientific, OH, USA.
³ Impel NeuroPharma, WA, USA.
⁴ Department of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, USA. Electronic address: Rutesh.Dave@liu.edu.

PMID: 34678275
DOI: 10.1016/j.xphs.2021.10.016

Abstract

The purpose of the present study was to prepare Orodispersible films (ODFs) loaded with ketoprofen nanoparticles (KT-NP). The Box-Behnken design was constructed in developing and optimizing the KTF-NP-ODFs. The effect of independent variables: Soluplus® concentration (X₁, stabilizer), Tween 80 concentration (X₂, surfactant), and KTF concentration (X₃, drug) were studied on the dependent variables: particle size (PS, Y₁), zeta potential (ZP, Y₂), and the polydispersity index (PDI, Y₃) of the NPs, as well as on the tensile strength (TS, Y₄) and permeability coefficient (PC, Y₅) of the KTF-NP-ODFs. Hydroxypropyl methylcellulose (HPMC E15) and polyethylene glycol (PEG 400) were used as the film former polymer and plasticizer, respectively, and their concentrations were kept constant for all formulations. KTF-NPs were prepared by antisolvent precipitation technology. This was followed by the addition of HPMC E15 and PEG 400 to prepare the ODFs using the solvent-casting method. The PS, PDI, and ZP for all the formulations were found in the range of 94 nm to 350 nm, 0.09 to 0.438, and -21.83 mV to -8.03 mV, respectively. The TS and PC of the prepared KTF-NP-ODFs were found between 1.21 MPa to 3.93 MPa and 3.12 × 10^-4 cm/h to 34.23 × 10^-4 cm/h, respectively. The amorphous nature of the KTF-NP in the ODFs was confirmed by the absence of characteristic crystalline peaks and endothermic events of KTF in X-ray diffraction (XRD) and modulated differential scanning calorimetry (mDSC), respectively. The optimized formulation showed ̴ 4 times higher permeability as compared to the pure KTF. In addition, the dissolution of pure KTF and the optimized KTF-NP-ODF in pH 1.2 at the end of 60 min was found to be ̴ 30% and ̴ 95%, respectively. Conclusively, KTF-NP-ODFs can be a promising drug delivery system to counter the issues related to dysphagia and bypass the common side effects, such as the gastric irritation associated with NSAIDs like KTF.

Keywords: Anti-solvent precipitation technology; Box-Behnken design; Design of experiments; Nanoparticles; Oro-dispersible films; permeability coefficient.

MeSH terms

Drug Delivery Systems
Excipients / chemistry
Ketoprofen*
Nanoparticles* / chemistry
Particle Size
Solubility

Substances

Excipients
Ketoprofen