Advanced Technologies for Oral Controlled Release: Cyclodextrins for oral controlled release

Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of inclusion complexes formation, with the following advantages for the drugs: (1) solubility, dissolution rate, stability and bioavailability enhancement; (2) to modify the drug release site and/or time profile; and (3) to reduce or prevent gastrointestinal side effects and unpleasant smell or taste, to prevent drug-drug or drug-additive interactions, or even to convert oil and liquid drugs into microcrystalline or amorphous powders. A more recent trend focuses on the use of CDs as nanocarriers, a strategy that aims to design versatile delivery systems that can encapsulate drugs with better physicochemical properties for oral delivery. Thus, the aim of this work was to review the applications of the CDs and their hydrophilic derivatives on the solubility enhancement of poorly water soluble drugs in order to increase their dissolution rate and get immediate release, as well as their ability to control (to prolong or to delay) the release of drugs from solid dosage forms, either as complexes with the hydrophilic (e.g. as osmotic pumps) and/ or hydrophobic CDs. New controlled delivery systems based on nanotechonology carriers (nanoparticles and conjugates) have also been reviewed

Study of the Complexation Behaviour of Fexofenadine with β-Cyclodextrin

Fexofenadine is a selective histamine H1 receptor antagonist, used for relief of the symptoms of allergy. However its aqueous solubility is very poor. Solid inclusion complexes of fexofenadine and β-cyclodextrin were prepared at the molar ratios of 1:1 and 1:2 by kneading, and coprecipitation methods to improve its solubility. Characterization of the complexes was performed using infrared spectroscopy, X-ray diffractometry, and in vitro dissolution studies. Fexofenadine was found to exhibit interaction with β-cyclodextrin both in solid and liquid state. Phase solubility studies indicated that fexofenadine forms a stable complex with β-cyclodextrin. Both IR spectroscopy and X-ray diffractometry studies indicated interaction of fexofenadine with β-cyclodextrin. Kneading method at 1:1 and co-precipitation method at 1:1 and 1:2 molar ratios showed significant interaction. In vitro dissolution studies confirmed the same results

Evaluation of Griseofulvin Binary and Ternary Solid Dispersions with HPMCAS

The stability and dissolution properties of griseofulvin binary and ternary solid dispersions were evaluated. Solid dispersions of griseofulvin and hydroxypropyl methylcellulose acetate succinate (HPMCAS) were prepared using the spray drying method. A third polymer, poly[N-(2-hydroxypropyl)methacrylate] (PHPMA), was incorporated to investigate its effect on the interaction of griseofulvin with HPMCAS. In this case, HPMCAS can form H bonds with griseofulvin directly; the addition of PHPMA to the solid dispersion may enhance the stability of the amorphous griseofulvin due to greater interaction with griseofulvin. The X-ray powder diffraction results showed that griseofulvin (binary and ternary solid dispersions) remained amorphous for more than 19 months stored at 85% RH compared with the spray-dried griseofulvin which crystallized totally within 24 h at ambient conditions. The Fourier transform infrared scan showed that griseofulvin carbonyl group formed hydrogen bonds with the hydroxyl group in the HPMCAS, which could explain the extended stability of the drug. Further broadening in the peak could be seen when PHPMA was added to the solid dispersion, which indicates stronger interaction. The glass transition temperatures increased in the ternary solid dispersions regardless of HPMCAS grade. The dissolution rate of the drug in the solid dispersion (both binary and ternary) has significantly increased when compared with the dissolution profile of the spray-dried griseofulvin. These results reveal significant stability of the amorphous form due to the hydrogen bond formation with the polymer. The addition of the third polymer improved the stability but had a minor impact on dissolution

Effect of hydrophilic swellable polymers on dissolution enhancement of carbamazepine solid dispersions studied using response surface methodology

The objective of this work was to study dissolution enhancement efficiency and solid dispersion formation ability of hydrophilic swellable polymers such as sodium carboxymethyl cellulose (Na-CMC), sodium starch glycolate (SSG), pregelatinized starch (PGS), and hydroxypropylmethyl cellulose (HPMC) with carbamazepine using 32 full factorial design for each of the polymers. Solid dispersions of carbamazepine were prepared using solvent evaporation method with around 70% solvent recovery. The independent variables were the amount of polymer and organic solvent. The dependent variables assessed were percentage drug dissolved at various time points and dispersion efficiency (ie, in terms of particle size of solid dispersion). Solid dispersions were evaluated for percentage drug dissolved, wettability, differential scanning calorimetry, scanning electron microscopy, and angle of repose. Multiple linear regression of results obtained led to equations, which generated contour plots to relate the dependent variables. Similarity factor and mean dissolution time were used to compare dissolution patterns obtained in distilled water and simulated gastric fluid United States Pharmacopeia (USP) XXVI of pH 1.2. Maximum drug dissolution was obtained with polymer order Na-CMC>SSG>PGS>HPMC. Particle size of drug was reduced ≈ 10–15, 3–5, 5–7, and 10–25 times in Na-CMC, SSG, PGS, and HPMC solid dispersions, respectively; whereas wettability of solid dispersions was found in the order of Na-CMC>HPMC>PGS>SSG. Angle of repose was found to be in the range of 29° to 35° for all solid dispersions, which shows good flowability characteristics. HPMC showed increase in drug dissolution up to an optimized level; however, furthers increase in its concentration decreased drug dissolution