Study of the parameters influencing the co-grinding process for the production of meloxicam nanoparticles

Abstract

Co-grinding is a procedure for the preparation of nanoparticles in which the drug is ground together with one or more excipients. The grinding of meloxicam, a crystalline solid, together with amorphous polyvinylpyrrolidone (PVP) or semi-crystalline polyethylene glycol (PEG) as excipients, is expected to lead to a drastic reduction in particle size. We optimized meloxicam grinding using a three level full factorial response surface design. In the case of PVP the optimum co-grinding parameter set in our study proved to be a meloxicam to PVP-C30 ratio of 1:1, and a rotation frequency of 400 rpm. The best size reduction was achieved at a meloxicam to PEG 6000 ratio = 1:2 at a rotation frequency of 400 rpm: nanoparticles averaging d SEM = 174 nm in diameter and with a very narrow size distribution (standard deviation 35% of mean) were obtained. X-ray powder diffraction analysis indicated that the optimized products contained amorphous meloxicam nanoparticles in the PVP-C30 composition, although meloxicam nanocrystals could also be detected in the samples which contained PEG 6000. The dissolution properties were significantly increased under nasal conditions (pH 5.1, temperature 30°C), especially in the case of the amorphous product. Such dry powder systems can offer novel opportunities in systemic nasal drug delivery.

Adaptation of the quality by design concept in early pharmaceutical development of an intranasal nanosized formulation

“…There are several techniques with which to produce nanosized drug materials that can be differentiated between bottom-up and top-down technologies [11][12][13][14][15][16]. The bottom-up technologies start from molecules which are dissolved and precipitated (crystallized) in a controlled fashion to yield the desired particle size.…”

“…HA was applied to form a nasal gel sample for permeability, cytotoxicity and in vivo experiments. Figure 1 lists those methods which formed part of the development protocol [15,19].…”

Retinoic acid and hydrocortisone strengthen the barrier function of human RPMI 2650 cells, a model for nasal epithelial permeability

“…New formulations for systemic nasal drug delivery, like nanoparticles (Kürti et al 2011), also need to be screened for nasal cytotoxicity and epithelial permeability. RPMI 2650 cells may serve as a nasal in vitro model to test epithelial toxicity and permeability across the nasal barrier.…”

“…These conditions alter the extent of dissolution of an active agent in a pharmaceutical formulation and they need to be taken into consideration in nasal preparations (Kürti et al 2011). Ex vivo excised animal tissue models are frequently utilized for nasal drug absorption studies (Wadell et al 1999(Wadell et al , 2003Schmidt et al 2000).…”

Crystallinity changes of organic materials in pharmaceutical technology

“…This energy can be reduced by adding a suitable excipient and performing a co-grinding procedure ; Kürti et al 2011;). An appropriate additive also helps to prevent the aggregation of nanoparticles, lubricates the system, and increases the water solubility of the API.…”