Physicochemical Characterization and Drug Release Studies of Nilvadipine Solid Dispersions Using Water-Insoluble Polymer as a Carrier

Abstract

Nilvadipine solid dispersions were prepared by the solvent method using water-insoluble polymers, including low-substituted hydroxypropylcellulose, croscarmellose sodium, carmellose calcium, carmellose, and crospovidone. Differential scanning calorimetry and powder x-ray diffraction analysis showed that nilvadipine was present in an amorphous state in the solid dispersion obtained using crospovidone as a carrier. The degree of crystallinity of nilvadipine was dependent on the ratio of nilvadipine to crospovidone, and nilvadipine was present in an amorphous state when the ratio of nilvadipine to crospovidone was below one-half. Fourier transform infrared studies suggested the presence of hydrogen bonding between nilvadipine and crospovidone in the solid dispersion. Dissolution studies indicated that the maximum percentage of dissolution and dissolution rate constants were markedly increased in nilvadipine with crospovidone solid dispersion, compared with those of pure nilvadipine and physical mixtures. The dissolution rate of nilvadipine solid dispersion with crospovidone could be calculated by the Higuchi square root time equation.

Haste Makes Waste: The Interplay Between Dissolution and Precipitation of Supersaturating Formulations

“…In fact, other properly designed supersaturating formulations regulated by matrix diffusion (i.e., based on other waterinsoluble carriers) have recently been shown to exhibit similar advantageous kinetic solubility profiles where drug supersaturation is sustained in the absence of any crystallization inhibitor (15). Additional observations showing a more sustained supersaturation resulting from a more gradual drug release have also been reported for the dissolution of griseofulvin from synthetic hectorite (i.e., an insoluble swelling clay) (16) and nilvadipine from crosslinked PVP (17). These independent studies together provide strong supporting evidence that the rate of supersaturation generation plays an essential role in determining the level of transient solubility enhancement, thereby affecting the overall kinetic solubility profiles under nonsink dissolution conditions (note: the experimental and modeling verification of this effect of supersaturation generation rate will be discussed in the Section "DO NOT PUSH TOO FAR TOO FAST").…”

Solid-State Characterization and Dissolution Properties of Meloxicam–Moringa Coagulant–PVP Ternary Solid Dispersions

“…Numerous studies have reported arginine to enhance the dissolution of various drugs such as meloxicam (11), indomethacin (12), and lornoxicam (13). Exhaustive research has been carried out on dissolution enhancement of drugs using water-insoluble polymers such as crospovidone (14,15) and enteric polymers such as hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, Eudragit® L100 and S100 (16), and Eudragit® E (17,18). As a rule, inclusion of water-soluble carriers results in a fast release of the drug from the matrix, and a poorly soluble or insoluble carrier leads to a slower release of the drug from the matrix (19,20).…”

New Nanometric Solid Dispersions of Glibenclamide in Neusilin® UFL2

“…The improvement in dissolution behaviour of solid dispersions has been more frequently achieved by using soluble carriers (12). However, it is not infrequent that also insoluble carriers may favour the dissolution rate of poorly water-soluble drugs from solid dispersions (35,36). When the carrier is insoluble and not swellable and up to an appropriate drug-carrier proportion, one can suppose that drug controls the diffusion through the carrier, particularly when the drug exceeds the solubility of the carrier (37).…”