The influence of HPMC substitution pattern on solid-state properties
ABSTRACT The solid-state properties were studied for different batches of hydroxypropyl methylcellulose (HPMC). The batches had similar chemical composition, but different degree of heterogeneity with regard to the distribution of the substituents along the polymer chains. The glass transition temperature, Tg, was analysed using a new developed method where dynamic mechanic analysis, DMA, was performed in compression mode on compacts, utilizing a wedge-shaped probe. The method was verified by conventional DMA on films. Molecular interactions were studied using FT-IR. In addition, the water vapour sorption was determined by gravimetric measurements and the plasticization by water vapour was studied on film samples using DMA. The results revealed a linear relationship between increasing Tg and increasing percent glucose liberated after enzyme hydrolysis. The percent glucose liberated can in turn be considered to account for both the heterogeneity of the substituents and the total degree of substitution. The results indicated that more heterogeneously substituted cellulose derivatives and derivates with a lower degree of substitution had stronger interactions between polymer chains. As expected from these results, some small difference in the plasticization by water vapour could be detected. However, no significant differences were found in molecular interactions using FT-IR or in the sorption of water vapour. The correlation between heterogeneity in the distribution of the substituents and Tg is of much interest as heterogeneously substituted batches of HPMC have been previously shown to exhibit very different behaviour in solution and in gelling tablets.
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ABSTRACT: This work aimed first to prepare deproteinized natural rubber latex (DNRL) and investigate the properties of films after it was blended with various adhesive polymers: hydroxypropylmethyl cellulose (HPMC), methyl cellulose (MC), sodium carboxymethyl cellulose (SCMC), poly(vinyl alcohol) (PVA), poloxamer 407, and sodium alginate. The second aim was to identify the films that would be the best for medical and pharmaceutical applications. Dibutyl phthalate (DBP), diethyl phthalate, dibutyl sebacate, triethyl citrate, and glycerin (GLY) were used as plasticizers to improve the elasticity and adhesiveness of the novel materials. DNRL was prepared by proteolytic alcalase enzyme treatment, followed by centrifugation. The DNRL was virtually free of protein, produced no significant reaction in the rabbit skin irritation test, and formed a good elastic film, but it had low skin adhesive properties. Blending DNRL with several polymers produced better films with different elastic and adhesive properties. Moisture uptake and swelling tests indicated that its films provided increasing hydrophilicity when blended with several polymers. SEM showed homogeneous films, and water hydraulic permeability tests indicated some porosity in matrix films. Blending DNRL with HPMC or PVA and DBP or GLY produced films with the best potential for novel materials. FT-IR, DSC, and XRD studies indicated the compatibility of the blended ingredients. In conclusion, DNRL blends could be used suitably for medical and pharmaceutical applications.Industrial & Engineering Chemistry Research 10/2012; 51(41):13393-13404. · 2.24 Impact Factor
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ABSTRACT: The nicotine transdermal patches (NTPs) are available used for smoking cessation; however, they still should be developed for high efficacy and low cost. In this study, deproteinized natural rubber latex (DNRL) blended with hydroxypropylmethyl cellulose (HPMC) and dibutylphthalate (DBP) were used as matrix membrane for nicotine (NCT) delivery. Several techniques, i.e., FT-IR, XRD, DSC, and SEM were used to characterize the compatibility of each ingredient in the blended patches. A backing layer was used to protect NCT from volatilization. Five different types of backing layer were evaluated for their effects on in vitro release and skin permeation of NCT from the formulated matrix membranes. The backing layer with highest moisture vapor transmission rate (MVTR) and lowest oxygen transmission (OT) supposed to give higher NCT release and skin permeation due to increasing of skin hydration and its occlusive effect. The kinetic of in vitro release and permeation was demonstrated the monophasic slow release pattern which confirmed by first order and zero order kinetics, respectively. Therefore, the backing layer could be appropriated and used conveniently in the preparation of NTPs.Chemical Engineering Research and Design 07/2012; 90(7):906-914. · 2.28 Impact Factor
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ABSTRACT: Nanocrystal-based drug delivery systems provide important tools for ocular formulation development, especially when considering poorly soluble drugs. The objective of the study was to formulate ophthalmic, intraocular pressure (IOP) reducing, nanocrystal suspensions from a poorly soluble drug, brinzolamide (BRA), using a rapid wet milling technique, and to investigate their IOP reducing effect in vivo. Different stabilizers for the nanocrystals were screened (hydroxypropyl methylcellulose (HPMC), poloxamer F127 and F68, polysorbate 80) and HPMC was found to be the only successful stabilizer. In order to investigate both the effect of an added absorption enhancer (polysorbate 80) and the impact of the free drug in the nanocrystal suspension, formulations in phosphate buffered saline (PBS) at pH 7.4 and pH 4.5 were prepared. Particle size, polydispersity (PI), solid state (DSC), morphology (SEM) as well as dissolution behavior and the uniformity of the formulations were characterized. There was rapid dissolution of BRA (in PBS pH 7.4) from all the nanocrystal formulations; after one minute 100 percent of the drug was fully dissolved. The effect was significantly pronounced at pH 4.5, where the dissolved fraction of drug was the highest. The cytotoxicity of nanocrystal formulations to human corneal epithelial cell (HCE-T) viability was tested. The effects of the nanocrystal formulations and the commercial product on the cell viability were comparable. The intraocular pressure (IOP) lowering effect was investigated in vivo using a modern rat ocular hypertensive model and elevated IOP reduction was seen in vivo with all the formulations. Notably, the reduction achieved in experimentally elevated IOP was comparable to that obtained with a marketed product. In conclusion, various BRA nanocrystal formulations, which all showed advantageous dissolution and absorption behavior, were successfully formulated.International Journal of Pharmaceutics 03/2014; · 3.99 Impact Factor