Ethylcellulose development

Rekhi, G.S. and Jambhekar, S.S. (1995) Ethylcellulose - a polymer review. Drug Development and Industrial Pharmacy 21 61-77. 

Arias, J.L., Lopez-Viota, M., Ruiz, M.A., Lopez-Viota, J. and Delgado, A.V. (2007) Development of carhonyl iron/ ethylcellulose core/shell nanoparticles for biomedical applications. International Journal of Pharmaceutics, 339, 237-245. 

For use as a plastics material, in lacquers, or for the preparation of water-insensitive films or filaments, ethylcellulose of a relatively high degree of substitution (1.8-2.8) and the aralkyl ether, benzylcellulose (degree of substitution 1.4-2.5) have had the greatest commercial development. 

Effective product and process optimization play a prominent role in any successful scale-up study. As an illustration, this case study summarizes the initial development, and subsequent scale-up, of a Wurster process designed to facilitate the application of an aqueous ethylcellulose dispersion to drug-loaded pellets. At the same time, it was intended to deal, up front, with some of the idiosyncrasies of such a coating system that often influence the functionality of the final dosage form. 

The success of prolonged-release morphine prompted the development of prolonged-release formulations for other opioids, for example the matrix made of hydrophobic and hydrophilic matrix formers, for example on hydrocodeine (DHC retard with cetostearyl alcohol and hydroxyethyl-cellulose), oxycodone (oxygesic with stearyl alcohol and polyacrylate) and tramadol (tramundin with cetostearyl alcohol and ethylcellulose). By virtue of the oblong shape of hydrocodeine and tramadol tablets the prolonged-release tablets can be divided, whereby compared with whole tablets release from the divided tablets is slightly accelerated. The difference with these forms is that with increasing dose the release slows down. 

Enzyme micro-encapsulation is another alternative for sensor development, although in most cases preparation of the microcapsules may require extremely well-controlled conditions. Two procedures have usually been applied to microcapsule preparation, namely interfacial polymerization and liquid drying [80]. Polyamide, collodion (cellulose nitrate), ethylcellulose, cellulose acetate butyrate or silicone polymers have been employed for preparation of permanent micro capsules. One advantage of this method is the double specificity attributed to the presence of both the enzyme and the semipermeable membrane. It also allows the simultaneous immobilization of many enzymes in a single step, and the contact area between the substrate and the catalyst is large. However, the need for high protein concentration and the restriction to low molecular weight substrates are the important limitations to this approach. 

Martinac,A., Filipovic-Grcic, J.,Voinovich, D.,Perissutti, B., and Franceschinis, E. (2005), Development and bioadhesive properties of chitosan-ethylcellulose microspheres for nasal delivery, Int. I. Pharm., 291, 69-77. 

Research was undertaken to develop a controlled release tablet of naproxen using ethylcellulose and both methods of wet granulation and solid dispersion were compared for effectiveness. Naproxen level was kept constant at 16% while ethylcellulose content was varied from 6% to 28% in the formulations. While both methods were successful at producing formulations with drug release profiles of at least 12 hours, the amount of ethylcellulose required to prepare such formulations was 33% less using the solid dispersion method. While none of the formulations released 100% of the drug, a cumulative 88% of naproxen was released from the solid dispersion formulation, compared with 84% from the wet granulation formulation (50). 

In one paper by Kirsch and Drennen [62], three experiments were performed on coated tablets. In the first experiment, intact theophylline tablets coated with an ethylcellulose polymer were analyzed by acousto-optic tunable filter (AOTF) spectrometers. Tablets were coated with increasing levels of ethylcellulose to vary the dissolution profiles. After spectra were collected, the dissolutions were run on a U.S.P. Type II dissolution apparatus. The time required for 50% of the drug to enter solution was used as the measure of dissolution rate. Principal component (PC) regression was used to develop the calibration. This gave a SEE of 2.8 min, a coefficient of variation of 0.977, and a SEP of 6.6 min the time to 50% dissolution ranged from 48 to 93 min. 

The first dispersion marketed under the tradename Aquacoat by FMC (Princeton, NJ) is based on lOmPas ethylcellulose. A similar product is under development by Dow Chemical (Midland, MI)/Coiorcon (Orpington, U.K.). A cellulose acetate dispersion is presented under experimentation by FMC. Finally, FMC has commercialized a CAP redispersible powder for enteric coating (CAP hydrolyses slowly in an aqueous solution) as Aquateric (see Sect 5). 

Gupta R, Mukherjee B (2003) Development and in vitro evaluation of diltiazem hydrochloride transdermal patches based on povidone-ethylcellulose matrices. Drug Dev Ind Pharm 29 (l) l-7... 

Sengel CT, Hascicek C, Gonul N. Development and in-vitro evaluation of modified release tablets including ethylcellulose microspheres loaded with diltiazem hydrochloride. Journal of Microencapsulation. March 2006 23(2) 135-152. PubMed PMID 16754371. 

D NMR was used to characterize native and acid hydrolyzed ethylcellulose (EC), a Hercules product widely used as a film-former in ink and coatings applications and as a binder and filler in pharmaceutical applications. An important parameter in controlling the properties of ethylcellulose is the degree of substitution (DS) of ethyl functionalities on the cellulose backbone. NMR is one technique that was used to determine both the total and positional DS (ethylation at the 2,3 and 6 positions of the anhydroglucose unit (AGU)). This analysis requires complete hydrolysis of the sample, and an improved acid hydrolysis technique was developed for this application. Two-dimensional (2-D) NMR techniques were used to confirm peak assignments related to positional DS determinations that were previously made by comparison with standards. In addition, 2-D NMR methods were used to evaluate positional DS of native ethylcellulose prior to acid hydrolysis. A comparison of the analytical results for the acid hydrolysate and native polymer will be discussed. 

Previous positional DS determination of ethylcelluloses were performed on samples subjected to exhaustive acidic methanolysis and analyzed by 1-D NMR (17). This method required four days for the digestion of each sample, and assignments of the side chain methylene carbons bonded to C2, C3 and C6 were made by comparison with synthetically prepared reference materials. Recently, a faster digestion method was developed (as described in the Experimental section), and it was necessary to confirm that assignments (Figure 4) used to determine positional DS after acidic methanolysis method were still valid for samples digested in TFA solutions. 

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