Characterization of Binary Mixtures Consisting of Cross‐Linked High Amylose Starch and Hydroxypropylmethylcellulose Used in the Preparation of Controlled Release Tablets

Abstract

Cross-linked amylose starch (CLA), hydroxypropylmethylcellulose (HPMC), and HPMC/CLA matrices were prepared by direct compression. HPMC was used to slow down the enzymatic degradation of CLA matrices. CLA was either granulated alone and mixed with HPMC or cogranulated with the latter. Compaction characteristics of the powder, hydration and mechanical properties of the resulting matrices, as well as the release profiles of three model drugs were investigated. The results showed that wet granulation of CLA in the presence of 10% HPMC improved significantly the flow properties of the powder without compromising its compactibility. Both CLA and HPMC deformed mainly by plastic flow (yield pressures are 75 and 124 MPa, respectively), but CLA exhibited a stronger elastic component (elastic recoveries are 18.4 and 11.5%, respectively). The values of yield pressure increased linearly with the concentration of HPMC. The addition of HPMC to CLA slightly decreased the resistance to consolidation but the crushing force of the final compacts was found to be proportional to the HPMC concentration. Mechanical studies on swollen matrices revealed that CLA formed a stronger gel than HPMC or CLA/HPMC mixture, and swelling and erosion of the tablets increased with HPMC content and incubation time. The in vitro release kinetics of three model drugs (pseudeoephedrine sulfate, sodium diclofenac, and prednisone) showed a clear effect of drug solubility and presence of alpha-amylase in the dissolution medium on the release rate. The addition of HPMC to CLA protected the tablets against alpha-amylase hydrolysis and reduced the release rate of prednisone and sodium diclofenac. The release of pseudoephedrine sulfate was fast and independent of HPMC and occurred mainly by diffusion.

Membrane Formation and Drug Loading Effects in High Amylose Starch Tablets Studied by NMR Imaging

“…Higher drug solubility usually leads to faster drug release, [45][46][47] but the solubility is not the only factor. 10,45 In diffusion-controlled systems, the size of the drug also has a large influence on the release kinetics. 45 Figure 9B shows that the release is not related only to the water uptake since in this case a linear relationship between drug release and water uptake should be observed.…”

“…The use of starch in controlled-release systems is attractive because of its safety aspects. The main advantages of this type of system over other hydrophilic polysaccharides excipients reside in its limited erosion 9,10 and its restricted swelling. 2,4,[9][10][11] The restricted swelling is ascribed to the retrogradation of the starch molecule chains into their double helical structure.…”

“…The main advantages of this type of system over other hydrophilic polysaccharides excipients reside in its limited erosion 9,10 and its restricted swelling. 2,4,[9][10][11] The restricted swelling is ascribed to the retrogradation of the starch molecule chains into their double helical structure. 9 The starch retrogradation was evidenced by 13 C CP/MAS spectroscopy, [12][13][14] the hydration of the tablet led to the formation of B-type double helices conformation thereby creating new physical cross-linking points leading to the formation of an extended three-dimensional network in the wet tablets.…”

“…12,16 This membrane increases the stiffness of the swollen tablet 3 and hinders the swelling of the starch particles in the core of the tablet. 10 Furthermore, the membrane blocks the erosive effect of the amylase enzymes thereby preserving the shape and integrity of the tablets. 9 This membrane does not propagate to the core of the tablet which retains a coarse particulate texture.…”

Pharmaceutical significance of cellulose: A review

“…In addition to the cellulose derivatives, crosslinked high amylose starch (CLA), has been successfully used as a controlled release excipient for the preparation of solid dosage forms [156]. Rahmouni et al characterized the gel matrix properties of binary mixtures of CLA/ HPMC, and evaluated the effect of incorporated HPMC on the release kinetics of three model drugs of different solubilities such as pseudoephedrine sulfate (very soluble), sodium diclofenac (sparingly soluble), and prednisone (very slightly soluble) [157]. Swelling characteristics and erosion of granulated crosslinked high amylose starch (CLAgr)/ HPMC tablets were found to increase with HPMC concentration and incubation time.…”