Diclofenac nanosuspensions: influence of preparation procedure and crystal form on drug dissolution behaviour.
The aim of this paper was to ascertain the role of drug crystalline form and preparation procedure in nanosuspension formulations in order to optimise dissolution properties of lipophilic, poorly soluble drugs, thus improving their oral bioavailability. The non-steroidal anti-inflammatory drug diclofenac acid (DCF), which is known to exist in different crystal forms, was chosen as a model drug. To this purpose, the influence of homogenization technique was studied by preparing several nanosuspensions with two different crystalline forms of the drug (DCF1 and DCF2). Particle size and size distribution, morphology, microstructure, and thermal behaviour of the different formulations were studied by photon correlation spectroscopy (PCS), scanning electron microscopy (SEM), X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC). Solubility studies of the bulk drug crystalline forms and dissolution experiments of nanosuspensions in comparison with different controls (bulk drug, physical mixtures, coarse suspensions) were carried out in different media: distilled water, simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Besides well known factors capable of affecting drug nanoparticle dissolution, results showed that drug dissolution rate in nanosuspensions is strongly affected by the drug solubility, which depends on the crystal form, and preparation procedure (high pressure homogenization process). Results demonstrated that this process partially transformed DCF2 in DCF1 while it did not have any effect on the DCF1 crystals.
Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Cagliari, Via Ospedale 72, 09124 Cagliari, Italy.
Francesco
F
Lai
Chiara
C
Sinico
Guido
G
Ennas
Francesca
F
Marongiu
Giaime
G
Marongiu
Anna Maria
AM
Fadda
D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004008:Diclofenac / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D005612:Freeze Drying; D006863:Hydrogen-Ion Concentration; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D012995:Solubility; D013535:Suspensions / Q000138:chemical synthesis / Q000737:chemistry*; D044366:Transition Temperature; D014961:X-Ray Diffraction
D013535:Suspensions; D020442:Poloxamer; D004008:Diclofenac