Garnpimol C. Ritthidej

Effect of Water-Soluble Carriers on Dissolution Characteristics of Nifedipine Solid Dispersions

Solid dispersions of nifedipine (NP) with polyethylene glycols (PEG4000 and PEG6000), hydroxypropyl-β-cyclodextrin (HPβCD), and poloxamer 407 (PXM 407) in four mixing ratios were prepared by melting, solvent, and kneading methods in order to improve the dissolution of NP. The enhancement of the dissolution rate and the time for 80% NP dissolution T80% depended on the mixing ratio and the preparation method. The highest dissolution rate and the T80% as short as 15 min were obtained from PXM 407 solid dispersion prepared by the melting method at the mixing ratio of 1:10. The X-ray diffraction (XRD) patterns of solid dispersions at higher proportions of carriers demonstrated consistent with the results from differential scanning calorimetric (DSC) thermograms that NP existed in the amorphous state. The wettability and solubility were markedly improved in the PXM 407 system. The presence of intermolecular hydrogen bonding between NP and PEGs and between HPβCD and PXM 407 was shown by infrared (IR) spectroscopy.

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.

Chitin and Chitosan as Disintegrants in Paracetamol Tablets

AbstractChitin and chitosan as disintegrants in paracetamol tablets were evaluated and compared to four commonly used disintegrants. Tablets containing chitosan showed faster disintegration, greater dissolution and was slightly softer than those containing chitin. An increment in concentration of these polymers caused markedly faster disintegration and better dissolution while an increase in compressional force showed opposite effects. Aging slightly altered the disintegration and dissolution. Tablets containing 7% of chitosan disintegrated within one minute which was much faster than those containing corn starch and microcrystalline cellulose but slightly slower than those containing sodium starch glycolate and croscamellose sodium. However, their dissolution profiles were non-significantly different from those of the latter ones.Crystallinity, degree of acetylation, chain length and particle size were attributed to the efficiency of chitin and chitosan. Moisture sorption and water uptake were found to b...

Sustained-release from Layered Matrix System Comprising Chitosan and Xanthan Gum

ABSTRACT Sustained-release tablets of propranolol HCl were prepared by direct compression using chitosan and xanthan gum as matrix materials. The effective prolongation of drug release in acidic environment was achieved for matrix containing chitosan together with xanthan gum which prolonged the drug release more extensive than that containing single polymer. Increasing lactose into matrix could adjust the drug release characteristic by enhancing the drug released. Component containing chitosan and xanthan gum at ratio 1:1 and lactose 75% w/w was selected for preparing the layered matrix by tabletting. Increasing the amount of matrix in barrier or in middle layer resulted in prolongation of drug release. From the investigation of drug release from one planar surface, the lag time for drug release through barrier layer was apparently longer as the amount of barrier was enhanced. Least square fitting the experimental dissolution data to the mathematical expressions (power law, first order, Higuchis and zero order) was performed to study the drug release mechanism. Layering with polymeric matrix could prolong the drug release and could shift the release pattern approach to zero order. The drug release from chitosan-xanthan gum three-layer tablet was pH dependent due to the difference in charge density in different environmental pH. FT-IR and DSC studies exhibited the charge interaction between of NH3+ of chitosan molecule and COO− of acetate or pyruvate groups of xanthan gum molecule. The SEM images revealed the formation of the loose membranous but porous film that was due to the gel layer formed by the polymer relaxation upon absorption of dissolution medium. The decreased rate of polymer dissolution resulting from the decreased rate of solvent penetration was accompanied by a decrease in drug diffusion due to ionic interaction between chitosan and xanthan gum. This was suggested that the utilization of chitosan and xanthan gum could give rise to layered matrix tablet exhibiting sustained drug release.

Chitosan citrate as film former: compatibility with water-soluble anionic dyes and drug dissolution from coated tablet.

Chitosan citrate solution containing 25% w/w propylene glycol was prepared and tested for its compatibility with some water soluble anionic dyes. The immiscibility between erythrosine, ponceau 4R, sunset yellow or tartrazine solutions and chitosan citrate solution was evident. The Fourier transform-infrared spectra revealed charged interaction between anionic dye and chitosan. Brilliant blue and green FS at concentration of 0.02-1.00% w/w polymer could be miscible with chitosan citrate solution due to the decrease in charge interaction by the positive charge on molecule of brilliant blue, which was also the composition in green FS. Propranolol HCl tablets coated with these colored film-coating solutions exhibited good appearance and no color migration. Drug dissolution from coated tablets was pH dependent, corresponding to the ability of chitosan to protonate in the medium. Color incorporation slightly retarded drug dissolution in acidic medium. Drug dissolved from coated tablet colored with brilliant blue was faster than from that colored with green FS. This was because brilliant blue had positive charge and more SO(3)H groups on its molecular structure, and exhibited higher water solubility. Accelerated condition could alter dissolution characteristics, and the Td+t(0) value from curve fitting between the dissolution profiles and Weibull equation was increased. However, drug dissolution from freshly prepared coated tablets, coated tablets after exposure to accelerated condition and after storage at room temperature for 12 months conformed to the monograph in USP XXIII.

DEVELOPMENT OF DICLOFENAC SODIUM CONTROLLED RELEASE SOLID DISPERSIONS BY SPRAY DRYING USING OPTIMIZATION STRATEGY I. POWDER FORMULATION

AbstractDiclofenac sodium (DS) controlled release solid dispersions were prepared by spray drying using ethylcellulose (EC), methacrylic acid copolymer (Eudragit), chitosan, hydroxypropyl methylcellulose (HPMC), and carbomer as single carriers and EC-chitosan as combined carriers. Among solid dispersions of 3:1 drugsingle carrier, the system containing chitosan exhibited the slowest dissolution followed by the systems containing Eudragit, EC, HPMC, and carbomer, respectively. Combined carriers of EC-chitosan exhibited more dissolution retarding effect than single carrier of EC or chitosan. An Hadamard matrix H[8] was employed to estimate the main effects of four parameters: spray feeding volume and contents of absolute ethanol, EC, and chitosan. Optimization strategy using multiple linear regression and a feasibility computer program was utilized to obtain the optimum quantities of the four parameters that would result in a required DS controlled release solid dispersion. The validation of the optimum DS ...

Mechanistic modeling of drug release from chitosan coated tablets.

A mechanistic model for drug release from tablets coated with chitosan was derived, assuming that: (1) core tablets are spherical and the drug dissolution is diffusion dependent. (2) In order for the drug release to occur, dissolution medium penetrates through the coated film and leaches out the drug through the film and the lag-time, t(lag) is set for these processes. (3) The coated film itself dissolves and becomes thinner with time. (4) After the film has completely dissipated and the undissolved core tablet becomes naked, drug release proceeds just as the spherical core tablet. Drug release rate was given as a differential equation. Model adaptation was carried out to the release data of propranolol hydrochloride tablets coated with chitosan and kept in different storage conditions. The goodness-of-fit of our model was better than any other conventional equations tested and estimated model parameters were informative.

Retained integrity of protein encapsulated in spray-dried chitosan microparticles.

Chitosan microparticles for delivery of proteins were prepared by spray-drying technique. The effects of formulation (molecular weight and concentration of chitosan) and process variables (inlet drying air temperature and spray rate) on size and morphology of microparticles were characterized. Size of microparticles was mainly controlled by formulation variables, while particle morphology was influenced by both formulation and process variables investigated in this study. Bovine serum albumin (BSA), as a model protein, was loaded into microparticles at different levels. BSA-loaded chitosan microparticles were characterized in terms of physicochemical properties and integrity of encapsulated protein, which was studied by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and circular dichroism. Size of microparticles ranged between 3.760–8.681 µm, of which BSA-loaded microparticles were larger in size than their corresponding blank microparticles. All microparticles showed dented or distorted surface, especially when BSA was incorporated, with positive surface charge exposed. Burst release of protein was observed. The effect was more pronounced as BSA loading level was increased. Integrity of entrapped protein could be retained when BSA was incorporated at high loading level. In conclusion, chitosan microparticles for delivery of protein could be efficiently prepared by spray-drying technique. The encapsulated protein was capable of retaining its integrity after the preparation process.

yCD/HPyCD mixtures as solubilizer: solid-state characterization and sample dexamethasone eye drop suspension.

PURPOSE Study the complexation of dexamethasone in combinations of γ-cyclodextrin (γCD) and 2-hydroxypropyl-γ-cyclodextrin (HPγCD) with emphasis on solid characterization and development of aqueous dexamethasone eye drop suspension for drug delivery through sclera. METHODS Dexamethasone/cyclodextrin (dexamethasone/CD) solid complex systems were prepared and characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and by in vitro drug dissolution testing. Sample eye drop suspensions were prepared applying solubilizer/suspender consisting of γCD/HPγCD mixtures, poloxamer 407 (P407) and polyvinylpyrrolidone. The eye drop suspension was characterized by its physicochemical properties. RESULTS The solid characterization techniques applied suggested that solid complexes were being formed. The results indicated that dexamethasone formed non-inclusion or micelle-like aggregates with HPγCD and the γCD/HPγCD mixture. The dissolution and dexamethasone release from the solid dexamethasone/γCD/HPγCD complexes was much faster than from the solid dexamethasone/γCD and dexamethasone/HPγCD complexes. The diameter of the solid particles in the dexamethasone eye drop suspension formulations were in all cases less than 10 μm with a mean diameter from 2.5 to 5.8 μm. The particle size decreased with increasing amount of P407. Permeation studies through semipermeable membrane and porcine sclera showed that increasing the amount HPγCD could enhance drug transport through the membrane barriers and this was related to enhanced drug solubility. The permeation rates were, however, decreased compared to formulation containing γCD alone due to larger hydrodynamic diameter of dexamethasone/γCD/HPγCD complex aggregates. All formulations were both chemically stable for at least 8 months at 25°C and 40°C. CONCLUSIONS Combination of γCD and HPγCD, i.e., formation of dexamethasone/γCD/HPγCD complexes, resulted in synergistic effect. That is the mixture had greater solubilizing effect than the individual CD, resulted in enhanced dissolution and drug delivery through membranes. Furthermore, it is possible to control the drug release rate by adjusting the γCD:HPγCD ratio in the solid dexamethasone/γCD/HPγCD complexes.

Deproteinized natural rubber film forming polymeric solutions for nicotine transdermal delivery

Film forming polymeric solutions were prepared from DNRL blended with MC, PVA, or SAG, together with dibutylphthalate or glycerine used as plasticizers. These formulations were easily prepared by simple mixing. In a preliminary step, in situ films were prepared by solvent evaporation in a Petri-dish. Their mechanical and physicochemical properties were determined. The in vitro release and skin permeation of nicotine dissolved in these blended polymers were investigated by a modified Franz diffusion cell. The formulations had a white milky appearance, and were homogeneous and smooth in texture. Their pH was suitable for usage in skin contact. The mechanical property of in situ films depended on the ingredients but all compatible films were in an amorphous phase. The DNRL/PVA was shown to be the most suitable mixture to form completed films. The in vitro release and skin permeation studies demonstrated a biphasic release that provided an initial rapid release followed by a constant release rate that fitted the Higuchi’s model. Nicotine loaded DNRL/PVA series were selected for the stability test for 3 months. These formulations needed to be kept at 4°C in tight fitting containers. In conclusion, film forming polymeric solutions could be developed for transdermal nicotine delivery systems.