Mucoadhesive Microspheres for Gastroretentive Delivery of Acyclovir: In Vitro and In Vivo Evaluation

The aim of the present investigation was to evaluate the potential use of mucoadhesive microspheres for gastroretentive delivery of acyclovir. Chitosan, thiolated chitosan, Carbopol 71G and Methocel K15M were used as mucoadhesive polymers. Microsphere formulations were prepared using emulsion-chemical crosslinking technique and evaluated in vitro, ex-vivo and in-vivo. Gelatin capsules containing drug powder showed complete dissolution (90.5 ± 3.6%) in 1 h. The release of drug was prolonged to 12 h (78.8 ± 3.9) when incorporated into mucoadhesive microspheres. The poor bioavailability of acyclovir is attributed to short retention of its dosage form at the absorption sites (in upper gastrointestinal tract to duodenum and jejunum). The results of mucoadhesion study showed better retention of thiolated chitosan microspheres (8.0 ± 0.8 h) in duodenal and jejunum regions of intestine. The results of qualitative and quantitative GI distribution study also showed significant higher retention of mucoadhesive microspheres in upper GI tract. Pharmacokinetic study revealed that administration of mucoadhesive microspheres could maintain measurable plasma concentration of acyclovir through 24 h, as compared to 5 h after its administration in solution form. Thiolated chitosan microsphere showed superiority over the other formulations as observed with nearly 4.0-fold higher AUC0–24 value (1,090 ± 51 ng h/ml) in comparison to drug solution (281 ± 28 ng h/ml). Overall, the result indicated prolonged delivery with significant improvement in oral bioavailability of acyclovir from mucoadhesive microspheres due to enhanced retention in the upper GI tract

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

Spray-dried mucoadhesive microspheres: Preparation and transport through nasal cell monolayer

The purpose of this research was to prepare spray-dried mucoadhesive microspheres for nasal delivery. Microspheres composed of hydroxypropyl methylcellulose (H), chitosan (CS), carbopol 934P (CP) and various combinations of these mucoadhesive polymers, and maltodextrin (M), colloidal silicon dioxide (A), and propylene glycol (P) as filler and shaper, were prepared by spray-drying technique. Using propranolol HCl as a model drug, microspheres were prepared at loadings exceedings 80% and yields between 24% and 74%. Bulky, free flowing microspheres that had median particle size between 15 and 23 μm were obtained. Their zeta potential was according to the charge of polymer. Adhesion time of mucoadhesive microspheres on isolated pig intestine was ranked, CS>CP: H>CP>H, while the rank order of swelling was CP>CS>H. Increasing the amount of CP in CP∶H formulations increased the percentage of swelling. Infrared (IR) spectra showed no interaction between excipients used except CS with acetic acid. The release of drug from CP and CP∶H microspheres was slower than the release from H and CS microspheres, correlated to their viscosity and swelling. Long lag time from the CP microspheres could be shortened when combined with H. The permeation of drug through nasal cell monolayer corresponded to their release profiles. These microspheres affected the integrity of tight junctions, relative to their swelling and charge of polymer. Cell viability was not affected except from CS microspheres, but recovery could be obtained. In conclusion, spray-dried microspheres of H, CS, CP, and CP∶H could be prepared to deliver drug through nasal cell monolayer via the opening of tight junction without cell damaging