IN VITRO DISSOLUTION OF CEPHALEXIN EXTEMPORANEOUS SUSPENSIONS

DURING SIX MONTHS OF STORAGE

Varillas MA, Brevedan MIV, Starkloff WJ, Gonzalez Vidal NL #

Ctedra Control de Calidad de Medicamentos, Departamento de Biologa, Bioqumica y Farmacia,

Universidad Nacional del Sur
San Juan 670 (B8000ICN) Baha Blanca, Argentina

INTRODUCTION
Most problems linked with extemporaneous suspensions are associated with physical stability. In general,
suspension stability studies consider only changes in chemical stability, pH, caking, and re-dispersability (1,
2), with no focus on dissolution stability (3).
Previous studies carried out on suspension dissolution do not consider changes during the administration
period of the constituted suspension (stored at room temperature as well as under refrigeration) throughout the
shelf life of the powdered product (4-10). During aging, absence of dissolution changes suggests that
bioavailability could remain intact (3).
Our research attempted to evaluate dissolution stability of three cephalexin extemporaneous suspensions from
Argentinian market, throughout the recommended administration period of constituted forms, during six
months of powders storage under natural and accelerated aging conditions (11).

MATERIALS AND METHODS

Two samples (B and C) of cephalexin extemporaneous suspensions (250mg/5mL) were purchased from
pharmacies in Baha Blanca city, a third sample (A) was produced by a local state laboratory.
Cephalexin content, dissolution profiles, pH, specific gravity and organoleptic characteristics were
determined (12-14) at constitution time, after 7 days of storage at room temperature and 14 days under
refrigeration, repeating this scheme at time zero, and throughout the storage of the powders for oral
suspension (3 and 6 months). The formulations were stored under ICH accelerated (40C/75% R.H.), and
natural conditions (25C/60% R.H.).
Dissolution profiles were compared in terms of Dissolution Efficiency (DE). Analysis of variance (ANOVA)
was used to compare both assay average results (chemical stability) and DE values (dissolution stability).

RESULTS
Color changes and unpleasant odor were observed during aging of all constituted suspensions, and pH values
remained in the range of 3.06.0, satisfying pharmacopoeia specifications.
Due to major changes in appearance after three months of storage under accelerated aging conditions, studies
could not be continued on sample A. Microbiological assays and chemical interaction tests are being
performed.
A cephalexin content decrease trend was observed during the administration period, throughout the storage of
powders, but in almost all cases the values were between 90.0-120.0%. For sample A, there were two assay
values lower than 90.0%, in accordance with the results of maximum percentage dissolved and DE, possibly
due to reconstitution volume.
In all cases, a 100.0% was dissolved in 5 minutes. Almost all DE values were above 100.0%, which indicates
an excellent dissolution performance. In some cases, statistical comparison showed differences between DE
values during the administration period of the suspension.

DISCUSSION / CONCLUSIONS
Cephalexin concentration remained within 90% of the initial value throughout the stability study, in all
brands. All samples showed a high dissolution rate with large dissolved percentages at early time points of the
dissolution profile. Although statistical differences were found between DE values throughout administration
period, they do not have an important clinical significance.

#
Corresponding author. Tel: +54 291 4595101 (int. 2441); e-mail: concal@uns.edu.ar
The constituted forms were chemically stable and had acceptable dissolution stability during the
administration period, throughout the powders aging study.

ACKNOWLEDGMENTS
This work was supported by funds from Universidad Nacional del Sur, Argentina (PGI 24/B139).

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