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ABHI.T.TURAKHIYA
M.Pharm Ceutics, CCPR.
Like A VERSETILE KEYSTROKER TOOL FOR FABRICATION OF THE FORMULATION: EUDRAGIT (Poly acrylate polymers)
The basic objective of controlled drug release is to achieve more effective therapies by eliminating the potential for both under- and overdosing. Other advantages are the maintenance of drug concentration within a desired range, fewer administrations, optimal drug use and increased patient compliance.
Eudragit prepared by the polymerization of acrylic and methacrylic acids or their esters, e.g., butyl ester or dimethylaminoethyl ester.
Eudragit has been introduced in USPNF, BP, PhEur, Hand book of pharmaceutical excipients.
EUDRAGIT polymers are copolymers derived from esters of acrylic and methacrylic acid, whose physicochemical properties are determined by functional groups (R).
EUDRAGIT polymers are available in a wide range of different physical forms (aqueous dispersion, organic solution, granules and powders).
A distinction between
1. Poly(meth) acrylates that are soluble in digestive fluids by salt formation: EUDRAGIT L, S, FS and E polymers with acidic or alkaline groups enable pH-dependent release of the active ingredient. 2. Poly(meth) acrylates that are insoluble but permeable in digestive fluids: EUDRAGIT RL and RS polymers with alkaline and EUDRAGIT NE polymers with neutral groups enable controlled release of the active ingredient by pH independent swelling.
Applications: From simple taste masking through gastric resistance to controlled drug release in all Applications: sections of the intestine. Delayed and sustained drug release
Methacrylic copolymers Functional group: carboxylic acid R = COOH (anionic) EUDRAGIT L 100/S 100/L 100-55 (powders) EUDRAGIT L 30 D-55 / FS 30 D (aqueous dispersion 30%) EUDRAGIT L 12,5 / S 12,5 (organic solution 12.5%) Gastroresistant and enterosoluble
I
CH3(H)
I I I
CH 3
I |
Aminoalkyl methacrylate copolymers Functional group: dimethyl aminoethyl R = COOCH2 CH2 N(CH3)2 (cationic) EUDRAGIT E 100 (granules) EUDRAGIT E 12,5 (organic solution 12.5%) EUDRAGIT E PO (powder) Gastrosoluble and enteroresistent
--- C CH C CH2--COO-Alquil R
Methacrylate copolymers Functional group: neutral esters R = COOCH3 or COOC4H9 (neutral) EUDRAGIT NE 30 D / 40 D / NM 30 D (aqueous dispersion 30% / 40% polymer content) Insoluble, permeable; pH-independent
Structure
S 100 S 12,5 FS 30 D
technical advantages: Aqueous processing Highly flexible coatings Suitable for multiparticulate tablet preparation
EUDRAGIT polymer E form Dissolution properties E 100 Granules E 12,5 12.5 % organic solution E PO Powder Soluble in gastric fluid up to pH 5.0 Swellable and permeable above pH 5.0
NE 30 D NE 40 D NM 30 D
Matrix
EUDRAGIT serves a matrix that embeds the active ingredient. The matrix structure is obtained by direct compression, granulation, or melt extrusion. EUDRAGIT NM 30 D is particularly suitable for granulation processes in the manufacture of matrix tablets.
Multiparticulate tablets :
EUDRAGIT is employed as a coating material, usually for the coating of pellets or particles that are filled into capsules or compressed into tablets. These pellets or particles act as diffusion cells in the digestive tract and release a constant drug quantity per unit of time (multi-unit dosage forms).
An ideal buccal film should be flexible, elastic, and soft yet strong enough to withstand breakage due to stress from activities in the mouth. So it must possess good mucoadhesive strength so that it is retained in the mouth for the desired duration. To prevent discomfort, swelling of the film should not be too extensive. The mechanical, bioadhesive, and swelling properties of buccal films are critical and must be evaluated. Various mucoadhesive devices, including tablets, films, patches, disks, strips ,ointments, and gels, have recently been developed. Eudragit providing good drug release barier with good adhesive strength.
Gene Delivery
Many hereditary diseases, acquired diseases such as multigenetic disorders and caused by viral genes could be treated by genetic therapy. Nanoparticles prepared by blending PLGA with methacrylate copolymer (Eudragit(R) E100) can efficiently and safely deliver plasmid DNA encoding mouse interleukin-10 leading to prevention of autoimmune diabetes44. New Anionic nanoparticles were prepared by Eudragit L100/55 provide a versatile platform for protein surface adsorption and a promising delivery system particularly when the maintenance of the biologically active conformation is required for vaccine efficacy. Antisense oligodeoxynucleotides were successfully delivered by nanoparticles prepared by Eudragit RL100, RS100.
Vaccine Delivery
Anionic surfactant-free polymeric core-shell nanospheres and microspheres were prepared by Eudragit L100-55. Vaccines were administered by different routes: intramuscular, subcutaneous or intranasal and the results were compared to immunization with Tat alone or with Tat delivered with the alum adjuvant. The data says that the nano and microspheres/ Tat formulations are safe and induce robust and long-lasting cellular and humoral responses after systemic and/or mucosal immunization.
Organisc SR Coating:
Case studies: Scale-up Study of Metoprolole Succinate Matrix Tablets using EUDRAGIT RS 30 D
The purpose of this study was the scaleup of a wet granulation process and the manufacturing of a matrix tablet using EUDRAGIT RS in combination with metoprolole succinate. Metoprolole succinate is freely soluble; and as beta-blocker it is often formulated to sustained release applications. Emcompress was used as filler since it is chemically and physically inert and therefore ideal to show the properties of the polymer. As polymers, a combination of EUDRAGIT RS PO and EUDRAGIT RS 30 D was used. For better agglomeration, plasticizer was added to the polymer suspension in a higher quantity compared to standard coating formulations.
RESULTS
The study shows a successful scale-up of the formulation from 0.5 kg lab to 90 kg production scale. Tablets with similar properties and dissolution profiles were manufactured in all scales. The knowledge about equipment and process enabled to adjust parameters from lab to production scale. The standard deviation in the dissolution test is very small, meaning the scale-up leads to very homogenous tablets in all scales. The release profiles after 6 months storage under ICH conditions are comparable. SEM analysis shows homogenous tablets in surface and cross section.
Quality By Design
Monograph:
EUDRAGIT RL 100, EUDRAGIT RL PO, EUDRAGIT RS 100 and EUDRAGIT RS PO
Conclusion:
The large variety of applications as well as the steadily increasing number of research workers engaged in studies of Eudragit polymers due to their unique properties, have made significant contributions to many types of formulations and suggest that the potential of Eudragit as novel and versatile polymer will be even more significant in future.
References:
Eudragit.evonic.com Eudragit a versatile polymer : a review By Vikrant K Nikam et al., Pharmacologyonline 1: 152-164 (2011) Jain SK, Chourasia MK, Dengre R.,Ind. J. Pharm. Sci. 2005; 67:43-50. Handbook of Excipient, 5th Ed. 563-570