Effect of chitosan salts and molecular weight on a nanoparticulate carrier for therapeutic protein

10.1081/PDT-200054388Pharmaceutical Development and Technology102189-196PDTE

Characterization of chitosan acetate as a binder for sustained release tablets

10.1016/j.jconrel.2004.06.008Journal of Controlled Release99115-26JCRE

Characterization of Chitosan Acetate as a Binder for Sustained Release Tablets

Abstract A chitosan derivative as an acetate salt was successfully prepared by using a spray drying technique. Physicochemical characteristics and micromeritic properties of spray-dried chitosan acetate (SD-CSA) were studied as well as drug-polymer and excipient-polymer interaction. SD-CSA was spherical agglomerates with rough surface and less than 75 Am in diameter. The salt was an amorphous solid with slight to moderate hygroscopicity. The results of Fourier transform infrared (FTIR) and solidstate 13 C NMR spectroscopy demonstrated the functional groups of an acetate salt in its molecular structure. DSC and TGA thermograms of SD-CSA as well as FTIR and NMR spectrum of the salt, heated at 120 8C for 12 h, revealed the evidence of the conversion of chitosan acetate molecular structure to N-acetylglucosamine at higher temperature. No interaction of SD-CSA with either drugs (salicylic acid and theophylline) or selected pharmaceutical excipients were observed in the study using DSC method. As a wet granulation binder, SD-CSA gave theophylline granules with good flowability (according to the value of angle of repose, Carr's index, and Hausner ratio) and an excellent compressibility profile comparable to a pharmaceutical binder, PVP K30. In vitro release study of theophylline from the tablets containing 3% w/w SD-CSA as a binder demonstrated sustained drug release in all media. Cumulative drug released in 0.1 N HCl, pH 6.8 phosphate buffer and distilled water was nearly 100% within 6, 16 and 24 h, respectively. It was suggested that the simple incorporation of spray-dried chitosan acetate as a tablet binder could give rise to controlled drug delivery systems exhibiting sustained drug release.

Priprava i vrednovanje tableta metoprolol tartarata s odgođenim i produljenim oslobađanjem koristeći hidrofilne polimere koji bubre

In view of the circadian rhythm of cardiovascular diseases, a delayed-onset extended-release (DOER) formulation of metoprolol tartrate (MT) was prepared. This was achieved through dissolution-guided optimization of the proportion of Methocel K4M and Methocel K15M. Core erosion ratio was greater than 50 %, thereby showing steady release of the drug after the lag time until complete dissolution. Optimized formulation produced a lag phase of 6 h followed by complete release of 98.7 ± 2.1 % in 24 h. Water uptake study revealed that Methocel K15M has lower water uptake (30 ± 1 %) than methocel K4M (40 ± 2 %) after 24 h. Axial swelling of polymers was higher than swelling in the radial direction. Drug-polymer interaction study precludes any interaction between drug and polymer. Such a drug delivery system may provide a viable alternative for effective management of hypertension and other related disorders. This work also proposes an approach to attain DOER for a hydrophilic drug by using a hydrophilic swellable polymer in press coat.Vodeći računa o cirkadijanom ritmu kardiovaskularnih bolesti, pripravljene su formulacije metoprolol tartarata (MT) s odgođenim i produljenim oslobađanjem (DOER). Optimizacija je provedena praćenjem oslobađanja pri čemu je mijenjan omjer hidroksipropilmetil celuloza Methocela K4M i Methocela K15M. Erozija obložnog sloja bila je veća od 50 %, što pokazuje ujednačeno oslobađanje ljekovite tvari nakon početne odgođene faze do potpunog oslobađanja. U optimiziranoj formulaciji oslobađanje je započelo nakon 6 h, nakon čega slijedi potpuno oslobađanje (98.7 ± 2.1 %) tijekom 24 h. Nakon 24 h ulazak vode u Methocel K15M bio je manji (30 ± 1 %) nego u Methocel K4M (40 ± 2 %). Aksijalno bubrenje polimera bilo je značajnije nego radijalno bubrenje. Nije zapažena interakcija lijeka i polimera. Opisani sustav za isporuku lijekova može biti korisna alternativa za učinkovitu terapiju hipertenzije i srodnih poremećaja. DOER s ovojnicom od hidrofilnih polimera koji bubre upotrebljiv je i za druge hidrofilne lijekove

Effects of Spray Drying on Physicochemical Properties of Chitosan Acid Salts

The effects of spray-drying process and acidic solvent system on physicochemical properties of chitosan salts were investigated. Chitosan used in spray dryings was obtained by deacetylation of chitin from lobster (Panulirus argus) origin. The chitosan acid salts were prepared in a laboratory-scale spray drier, and organic acetic acid, lactic acid, and citric acid were used as solvents in the process. The physicochemical properties of chitosan salts were investigated by means of solid-state CP-MAS 13C nuclear magnetic resonance (NMR), X-ray powder diffraction (XRPD), differential scanning calorimetry, and Fourier transform infrared spectrometry (FTIR) and near-infrared spectroscopy. The morphology of spray-dried chitosan acid salts showed tendency toward higher sphericity when higher temperatures in a spray-drying process were applied. Analysis by XRPD indicated that all chitosan acid salts studied were amorphous solids. Solid-state 13C NMR spectra revealed the evidence of the partial conversion of chitosan acetate to chitin and also conversion to acetyl amide form which appears to be dependent on the spray-drying process. The FTIR spectra suggested that the organic acids applied in spray drying may interact with chitosan at the position of amino groups to form chitosan salts. With all three chitosan acid salts, the FTIR bands at 1,597 and 1,615 cm−1 were diminished suggesting that –NH groups are protonated. The FTIR spectra of all chitosan acid salts exhibited ammonium and carboxylate bands at 1,630 and 1,556 cm−1, respectively. In conclusion, spray drying is a potential method of preparing acid salts from chitosan obtained by deacetylation of chitin from lobster (P. argus) origin