Results and discussion
Eudragit polymers enabled the authors to produce tablets with excellent hardness. The crushing strength of the tablets and
their friability are summarized in Table V.
Table III: Batch of 1500 matrix tablets with methacrylic copolymers (Eudragit FS 30 D).
The release profiles of bupropion hydrochloride from the tablets prepared using different ionic grades of Eudragit at initial
conditions and under three months' accelerated stability conditions are shown in Figures 2–4.
The matrix tablets formed with Eudragit polymers were sufficiently integrated and uniform to control the release of the highly
soluble drug over 8 h, thus complying with USP specifications. Because it is a neutral polymer, Eudragit NM 30 D is compatible with most active ingredients. During the
development of bupropion tablets with Eudragit NM 30 D, the authors added Eudragit RS PO, another strong retardant, to the
solid form. This addition led to even stronger retardation without increasing water quantity during the process.
Similar dissolution results were observed when the neutral polymer was replaced with anionic polymer Eudragit FS 30 D. At
a 15% concentration, the USP matching profile was attained at initial and accelerated stability conditions.
Table IV: Batch of 1500 matrix tablets with methacrylic copolymers (Eudragit RS PO).
When the authors dispersed the cationic powder grade Eudragit RS PO into a hydroalcoholic medium, the tablet achieved the
USP matching profile with 40% polymer concentration at the initial and the accelerated stability conditions.
Assay of bupropion hydrochloride.
Bupropion hydrochloride content in the tablets manufactured with different ionic grades of Eudragit was analyzed at the initial
and at the end of three months' accelerated stability conditions. The results of the content are given in Table VI.
The assay results confirmed the quality of all matrix tablets tested. The drug stayed stable in the polymer matrix without
any degradation over time.
Ethanol resistance test.
Five years ago, FDA became vigilant following an incident of ethanol consumption associated with a marketed analgesic preparation.
Modified-release formulations of this analgesic with a reasonably narrow therapeutic index have been coming under scrutiny.
FDA's Guidance for Industry: Individual Product Bioequivalence Recommendations contains a list of controlled-release formulations for which in vitro dissolution testing in hydroalcoholic media is required (7). The list includes extended-release bupropion hydrochloride tablets.
In fact, if the reference listed product is rugged and no labeling cautions are warranted, it would be highly desirable for
any generic product to be similarly robust, even if its modified-release mechanism were different from that of the innovator
The comparative release profiles of matrix tablets with Eudragit polymers in 0.1 N HCl and 40% ethanolic 0.1 N HCl are shown
in Figures 5–7.
No investigated matrix formulations showed a significant difference between the medium without and with 40% alcohol content.
The marketed product shares this characteristic. The similarity factor F2, which denotes the closeness between the dissolution
values of the in-house formulation and the marketed product, was more than 60. Hence, all tested Eudragit matrix formulations
fulfilled the FDA recommendation for robust formulations that prevent alcohol dose dumping.
Table V: Hardness and friability data of trials with different grades of methacrylic copolymers (Eudragit).