Pharmaceutical Technology: Controlled Drug Release, Volume 2

24 MATRIX FORMULATIONS [CH. 2
MATERIALS AND METHODS
The HPMC was manufactured by Dow Chemicals (USA) as Methocel K15M and Methocel K100
grades. All solutes were of laboratory reagent standard obtained from British Drug Houses (Poole,
UK) and all drugs were BP standard or better.
Cloud point studies
Quantities of gel (50 g) were prepared to contain 2% HPMC by dispersing the polymer into
approximately 33% of the total weight of distilled water previously heated to 80°C, adding the
required electrolyte or drug dissolved in distilled water and making up to weight. The gels were
stored overnight to hydrate fully. Samples for analysis were transferred to disposable 1 cm 2
cuvettes and any air bubbles were removed by centrifugation. Samples were slowly heated and
readings taken, initially at 5°C intervals but reducing to 1°C increments near the cloud points. The
samples were measured spectrophotometrically at 800 nm against a 2% aqueous solution of the gel.
For studies on the effect of pH on the cloud point gels were prepared without added electrolyte.
Their pH was adjusted with 1 M HCl or 1 M NaOH following overnight hydration.
Disintegration studies
Shallow convex tablets ( in) containing 300 mg HPMC K15M and 1% magnesium stearate were
prepared by direct compression. Disintegration tests were performed in triplicate, using the BP
1988 method, in 600 ml of media at 37°C using discs. Tests were run for a maximum of 2 h.
Dissolution studies
Shallow convex tablets ( in) containing 160 mg propranolol hydrochloride, 140 mg HPMC K15M
and 1% magnesium stearate were prepared by direct compression. Three tablets were tested into
1l of dissolution fluid buffer at 37°C using the British Pharmacopoeia (1988) basket method,
rotating at 100 rev min −1 andmonitoring propranolol at 288 nm. All media were prepared in molar
concentrations and contained only the electrolyte stated. When the pH of the media was adjusted
to pH 6±0.2 either 1 M HCl or 1 M NaOH was used which did not significantly increase the ionic
strength of the media.
The ionic strengths, I, of the solutions used for cloud point, disintegration and dissolution fluids
were calculated according to equation (1):
where m is the molarity and z is the valence of each ion in the solution. Differences between
molarity were considered to be too small to be significant.
(1)