Influence of Formulation Parameters on Redispersibility of Naproxen Nanoparticles from Granules Produced in a Fluidized Bed Process

Abstract

The particle size reduction of active pharmaceutical ingredients is an efficient method to overcome challenges associated with a poor aqueous solubility. With respect to stability and patient’s convenience, the corresponding nanosuspensions are often further processed to solid dosage forms. In this regard, the influence of several formulation parameters (i.e., type of carrier material, type and amount of additional polymeric drying excipient in the nanosuspension) on the redispersibility of naproxen nanoparticle-loaded granules produced in a fluidized bed process was investigated. The dissolution rate of the carrier material (i.e., sucrose, mannitol, or lactose) was identified as a relevant material property, with higher dissolution rates (sucrose > mannitol > lactose) resulting in better redispersibility of the products. Additionally, the redispersibility of the product granules was observed to improve with increasing amounts of polymeric drying excipient in the nanosuspension. The redispersibility was observed to qualitatively correlate with the degree of nanoparticle embedding on the surface of the corresponding granules. This embedding was assumed to be either caused by a partial dissolution and subsequent resolidification of the carrier surface dependent on the dissolution rate of the carrier material or by resolidification of the dissolved polymeric drying excipient upon drying. As the correlation between the redispersibility and the morphology of the corresponding granules was observed for all investigated formulation parameters, it may be assumed that the redispersibility of the nanoparticles is determined by their distance in the dried state.

Exploring the performance-controlling tablet disintegration mechanisms for direct compression formulations

“…For example, lactose and mannitol have very similar absolute solubility values (1 g in 5.24 mL and 1 g in 5.5 mL, respectively, for water at 20 • C (Rowe et al, 2009)), however, the rates at which these excipients dissolve are different. This was previously shown through determining the intrinsic dissolution rates by Wewers et al (2020), and further supported by the single particle dissolution analysis performed for lactose and mannitol (Section 3.1). The difference in filler dissolution rate is evident when comparing the disintegration time of tablets containing MCC/mannitol and MCC/lactose (Fig 2).…”

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“…It has various advantages over conventional trial and error method like decreased number of trials and estimation of interactions and statistical approach in getting the ideal formulation. [8,9] Naproxen is a widely used NSAID (nonsteroidal antiinflammatory drug) in various conditions of inflammation such as arthritis. It has its applications in the treatment of rheumatoid arthritis, spondylitis, gout, migraine, etc.…”

Amorphization and modified release of ibuprofen by post-synthetic and solvent-free loading into tailored silica aerogels

“…However, upon oral administration of a solid dosage form, the dissolution rate of the drug in the gastrointestinal tract fluids limits the extent of absorption by the intestinal mucosa and thus its pharmaceutical effect. Consequently, numerous novel formulation approaches have been developed and utilized to overcome this challenge (Singh et al., 2018 ; Melzig et al., 2018a , b ; Suresh et al., 2020 ; Wewers et al., 2020 ; Steiner et al., 2021 ). To this end, the conversion of a thermodynamically stable crystal structure to a high-energy amorphous form of an API constitutes a promising procedure in order to increase its solubility, dissolution rate and thus the oral bioavailability.…”