Abstract
On the basis of their large specific surface areas, high adsorption and cation exchange capacities, swelling potential and low toxicity, natural smectite clays are attractive substrates for the gastric protection of neutral and cationic drugs. Theophylline is an amphoteric xanthine derivative that is widely used as a bronchodilator in the treatment of asthma and chronic obstructive pulmonary disease. This study considers the in vitro uptake and release characteristics of the binary theophylline-smectite system. The cationic form of theophylline was readily ion exchanged into smectite clay at pH 1.2 with a maximum uptake of 67 ± 2 mg g−1. Characterisation of the drug-clay hybrid system by powder X-ray diffraction analysis, Fourier transform infrared spectroscopy, differential scanning calorimetry and scanning electron microscopy confirmed that the theophylline had been exclusively intercalated into the clay system in an amorphous form. The drug remained bound within the clay under simulated gastric conditions at pH 1.2; and the prolonged release of approximately 40% of the drug was observed in simulated intestinal fluid at pH 6.8 and 7.4 within a 2-h timeframe. The incomplete reversibility of the intercalation process was attributed to chemisorption of the drug within the clay lattice. These findings indicate that smectite clay is a potentially suitable vehicle for the safe passage of theophylline into the duodenum. Protection from absorption in the stomach and subsequent prolonged release in the small intestine are advantageous in reducing fluctuations in serum concentration which may impact therapeutic effect and toxicity.
Highlights
Aluminosilicate clays are widely used in the pharmaceutical industry as stabilising and suspending agents, rheology modifiers and texture enhancers in various dosage forms [1, 2]
The theophylline-smectite hybrid selected for the in vitro release study was prepared by the batch sorption method described above using 50 mg cm−3 of smectite suspended in 0.1 N HCl(aq) containing 3 mg cm−3 of theophylline at 50 °C for 60 min
In vitro release of theophylline from the drug-clay hybrid was monitored in phosphate-buffered saline (PBS) at pH 7.4 [11], simulated gastric fluid (SGF) at pH 1.2 [12] and simulated intestinal fluid (SIF) at pH 6.8 and 7.4 [13]
Summary
Aluminosilicate clays are widely used in the pharmaceutical industry as stabilising and suspending agents, rheology modifiers and texture enhancers in various dosage forms [1, 2]. Lattice substitution of Mg2+ for Al3+ in montmorillonite, and Al3+ for Si4+ substitution in saponite, confers a negative charge on the layers which is balanced by labile interlayer Na+ and Ca2+ cations. In addition to the charge-balancing cations, water molecules are present between the layers, both of which are readily exchangeable. Montmorillonite, saponite and their mixtures are popular options in clay-drug hybrid controlled release systems for oral, transdermal and topical administration [1,2,3,4,5]. Cationic drugs are suitable for intercalation within these clays, as they are conveniently exchanged for the interlayer cations and their subsequent electrostatic interaction with the negatively charged layers extends their release. In addition to modified release, intercalation within the clay can afford protection from selected in vivo environments such as gastric acidity
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