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

Mucoadhesive bilayered tablets for buccal sustained release of flurbiprofen

The aim of this work was the design of sustained-release mucoadhesive bilayered tablets, using mixtures of mucoadhesive polymers and an inorganic matrix (hydrotalcite), for the topical administration of flurbiprofen in the oral cavity. The first layer, responsible for the tablet retention on the mucosa, was prepared by compression of a cellulose derivative and polyacrylic derivative blend. The second layer, responsible for buccal drug delivery, was obtained by compression of a mixture of the same (first layer) mucoadhesive polymers and hydrotalcite containing flurbiprofen. Nonmedicated tablets were evaluated in terms of swelling, mucosal adhesion, and organoleptic characteristics; in vitro and in vivo release studies of flurbiprofen-loaded tablets were performed as well

Chitosan and chitosan chlorhydrate based various approaches for enhancement of dissolution rate of carvedilol

<p>Abstract</p> <p>Background and the purpose of the study</p> <p>Carvedilol nonselective β-adrenoreceptor blocker, chemically (±)-1-(Carbazol-4-yloxy)-3-[[2-(o-methoxypHenoxy) ethyl] amino]-2-propanol, slightly soluble in ethyl ether; and practically insoluble in water, gastric fluid (simulated, TS, pH 1.1), and intestinal fluid (simulated, TS without pancreatin, pH 7.5) Compounds with aqueous solubility less than 1% W/V often represents dissolution rate limited absorption. There is need to enhance the dissolution rate of carvedilol. The objective of our present investigation was to compare chitosan and chitosan chlorhydrate based various approaches for enhancement of dissolution rate of carvedilol.</p> <p>Methods</p> <p>The different formulations were prepared by different methods like solvent change approach to prepare hydrosols, solvent evaporation technique to form solid dispersions and cogrind mixtures. The prepared formulations were characterized in terms of saturation solubility, drug content, infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), electron microscopy, <it>in vitro</it> dissolution studies and stability studies.</p> <p>Results</p> <p>The practical yield in case of hydrosols was ranged from 59.76 to 92.32%. The drug content was found to uniform among the different batches of hydrosols, cogrind mixture and solid dispersions ranged from 98.24 to 99.89%. There was significant improvement in dissolution rate of carvedilol with chitosan chlorhdyrate as compare to chitosan and explanation to this behavior was found in the differences in the wetting, solubilities and swelling capacity of the chitosan and chitosan salts, chitosan chlorhydrate rapidly wet and dissolve upon its incorporation into the dissolution medium, whereas the chitosan base, less water soluble, would take more time to dissolve.</p> <p>Conclusion</p> <p>This technique is scalable and valuable in manufacturing process in future for enhancement of dissolution of poorly water soluble drugs.</p

Solid-state and mechanical properties of aqueous chitosan-amylose starch films plasticized with polyols

The film-forming ability of chitosan and binary mixtures of chitosan and native amylose corn starch (Hylon VII) was evaluated with free films prepared by a casting/solvent evaporation method. Unplasticized and plasticized free chitosan films in aqueous acetic acid and respective films containing a mixture of chitosan and native amylose starch in acetic acid were prepared. Glycerol, sorbitol, and i-erythritol were used as plasticizers. Solid-state and mechanical properties of the films were studied by powder x-ray diffractometry (XPRD), differential scanning calorimetry (DSC), and a materials testing machine. The films composed of a mixture of chitosan and native amylose starch in acetic acid were clear and colorless. A plasticizer concentration of 20% wt/wt (of the polymer weight) ws sufficient to obtain flexible films with all samples tested. X-ray diffraction patterns and DSC thermograms indicated an amorphous state of the films independent of the type of plasticizer used. In conclusion, incorporation of native amylose com starch into chitosan films improves the consistency and the mechanical properties of the films

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

Formulation and Evaluation of Bioadhesive Buccal Drug Delivery of Tizanidine Hydrochloride Tablets

The study aim was concerned with formulation and evaluation of bioadhesive buccal drug delivery of tizanidine hydrochloride tablets, which is extensively metabolized by liver. The tablets were prepared by direct compression using bioadhesive polymers such as hydroxylpropyl methylcellulose K4M, sodium carboxymethyl cellulose alone, and a combination of these two polymers. In order to improve the permeation of drug, different permeation enhancers like beta-cyclodextrin (β-CD), hydroxylpropyl beta-cyclodextrin (HP-β-CD), and sodium deoxycholate (SDC) were added to the formulations. The β-CD and HP-β-CD were taken in 1:1 molar ratio to drug in formulations. Bioadhesion strength, ex vivo residence time, swelling, and in vitro dissolution studies and ex vivo permeation studies were performed. In vitro release of optimized bioadhesive buccal tablet was found to be non-Fickian. SDC was taken in 1%, 2%, and 3% w/w of the total tablet weight. Stability studies in natural saliva indicated that optimized formulation has good stability in human saliva. In vivo mucoadhesive behavior of optimized formulation was performed in five healthy male human volunteers and subjective parameters were evaluated