EVALUATION STABILITY OF THE PYRAZINAMIDE IN THE PRESENCE
OF EXCIPIENTS THROUGH THERMAL ANALYSIS AND ACCELERATED
STABILITY STUDY OF DIFFERENT FORMULATIONS.
RAFFIN, F.N.1, GOES, J.S.2, FREIRE, F.D.3, MOURA, T.F.A.L.1
1
Laboratório de Desenvolvimento de Medicamentos (LDM) - Departamento de Farmácia – CCS UFRN, Natal, Rio Grande do Norte, Brasil. E-mail: [email protected]
2
Laboratório de Desenvolvimento de Medicamentos (LDM) - Programa de Pós Graduação em Ciências
Farmacêuticas (PPgCF) - UFRN, Natal, Rio Grande do Norte, Brasil.
3
Programa de Pós Graduação em Desenvolvimento e Inovação Tecnológica em Medicamentos
(PPGDITM) - UFRN, Natal, Rio Grande do Norte, Brasil.
Keywords: Stability; Pyrazinamide; Lactose SuperTab; Mycrocristaline Cellulose; TG; DTA.
1. Introduction
Tuberculosis affects a third of the world
population, and Pyrazinamide (PZA) is one of
the drugs used in treatment, available in tablets
as dosage form. Among the excipients
commonly used in the production of tablets are
diluents, such as lactose supertab (LST) and
microcrystalline cellulose (MCC), which should
not negatively affect the stability of the drug.
Thermal analysis is found a good tool to verify
the compatibility between drug and excipient.
Furthermore,
stability
assessment
after
obtaining of the final product is important. The
aim of this work was to analyze the drugexcipient compatibility, as well as monitoring
the stability of the final dosage form.
2. Methods
- Thermal analysis: About 10 mg of binary
mixtures MCC-PZA (MB1) and LST-PZA
(MB2) at 1:1 ratio were placed in alumina
crucibles and analyzed with a Shimadzu DTG60 apparatus, which provides simultaneous data
curves thermogravimetric (TG) and differential
thermal analysis (DTA), under nitrogen
atmosphere at flow rate of 50 mL.min-1. The
temperature ranged from 35 to 900ºC with a
heating rate of 10°C.min-1.
- PZA tablets: Two formulations containing
PZA, magnesium stearate, croscarmellose
sodium and differing on the diluents type: MCC
(F1) and LST (F2) were performed by direct
compression in a rotative machine with 13 mm
punches. The tablets were enveloped in
aluminum foil and stored in a climatic chamber
(TECNAL, TE 4001) at 40°C and 75% relative
humidity. The tablets were evaluated by
physical-chemical tests determined by the
official compendia (Brazilian Pharmacopeia, 4th
ed. And USP 23) at initial time, after three and
six months.
3. Results
- Thermal analysis: MB2 TG curve did not
reproduce the events of mass loss observed in
the curves of PZA and LST alone, while in the
MB1 curve, these events can be identified.
Moreover, the MB2 DTA curve showed a
decrease in the PZA melting temperature; in
addition, the endothermic peaks could not be
summed, indicating an interaction between PZA
and LST (fig.1).
- Stability of PZA tablets: Results of hardness
and friability of F2 tablets were outside to the
specified value (<4.0 kg/cm2 and friability>
1.5%). Concerning the other analysis, F2 tablets
were found according specifications.
CURVAS DTA
DTA
uV
0.00
-100.00
PZA
LST
PZA + LST
-200.00
-300.00
-400.00
-0.00
200.00
400.00
600.00
Temp [C]
800.00
Figure 1: DTA curves of PZA-LST binary mixtures
4. Conclusion
The results indicated that the use of LST in the
formulations containing PZA should be
carefully assessed through additional assays and
monitoring the stability of the tablets. The
accelerated stability study showed no
degradation of PZA in the presence of LST. F1
showed better results when compared to F2.
Acknowledgments
UFRN; PROPESQ.