methylcellulose and Deglutition-Disorders

Evaluation of the potential for oral sustained drug delivery of formulations with in-situ gelling properties is the main objective of the present investigation. Oral administration of aqueous dispersion of sodium alginate (1.5% w/v) containing calcium ions in complex form resulted in the formation of gel matrix as a consequence of the release of the calcium ions in the acidic environment of stomach fluid. Addition of methylcellulose, sodium chloride and polyethylene glycol improved the drug retention efficacy of the gel. In this investigation, the study on the influence of added excipients on the rheological and drug release properties of the formulations has been focused. In-vitro studies demonstrated diffusion-controlled release of paracetamol from the gels. The bioavailability of orally administered paracetamol from the in-situ gel F4 (composed of 1.5% sodium alginate, 1.5% methyl cellulose, 3% CaCO

Topics: Acetaminophen; Administration, Oral; Alginates; Biological Availability; Deglutition Disorders; Delayed-Action Preparations; Drug Compounding; Drug Delivery Systems; Drug Liberation; Gels; Humans; Hydrogen-Ion Concentration; Kinetics; Methylcellulose; Polyethylene Glycols; Viscosity

The impact of demographic ageing is likely to be of major significance in the coming decades due to low birth rates and higher life expectancy. Older people generally require more prescribed medicines due to the presence of multiple conditions such as dysphagia which can make swallowing medicines challenging. This study involves the development, characterization and optimization of composite wafers for potential oral and buccal delivery of low dose aspirin to prevent thrombosis in elderly patients with dysphagia. Blank (BLK) wafers (no loaded drug) were initially formulated by dissolving combinations of metolose (MET) with carrageenan (CAR) and MET with low molecular weight chitosan (CS) in different weight ratios in water, to identify optimum polymer combinations. However, drug loaded (DL) wafers were prepared using 45% v/v ethanol to help complete solubilization of the aspirin. The formulations were characterized using texture analyzer (hardness, mucoadhesion), scanning electron microscopy (SEM), X-ray diffractometry (XRD), attenuated total reflectance - Fourier transform infrared (ATR-FTIR), differential scanning calorimetry (DSC), thermogravimetric analyzer (TGA), and swelling capacity. Wafers with higher total polymer concentration were more resistant to penetration (MET:CAR 1:1 samples B2, C2) and MET:CS 1:1 (sample E2) and MET:CS 3:1 (sample F2) and also depended on the ratios between the polymers used. From the characterization, samples C2, B2, E2 and F2 showed the most ideal characteristics. XRD showed that BLK wafers were amorphous, whilst the DL wafers were crystalline due to the presence of aspirin. SEM confirmed the presence of pores within the polymer matrix of the BLK wafers, whilst DL wafers showed a more compact polymeric matrix with aspirin dispersed over the surface. The DL wafers showed a good flexibility required for transportation and patient handling and showed higher swelling capacity and adhesion values with phosphate buffer saline (PBS) than with simulated saliva (SS). Drug dissolution studies showed that aspirin was rapidly released in the first 20 min and then continuously over 1 h. FTIR confirmed the interaction of aspirin with the polymers evidenced by peak shifts around 1750 cm

Topics: Aged; Aspirin; Carrageenan; Chemistry, Pharmaceutical; Chitosan; Deglutition Disorders; Drug Delivery Systems; Drug Liberation; Excipients; Fibrinolytic Agents; Freeze Drying; Humans; Methylcellulose; Polymers; Thrombosis

Elderly patients with swallowing dysfunction may benefit from the oral administration of liquid dosage forms with in situ gelling properties.. We have designed in situ gelling liquid dosage formulations composed of mixtures of methylcellulose, which has thermally reversible gelation properties and sodium alginate, the gelation of which is ion-responsive, with suitable rheological characteristics for ease of administration to dysphagic patients and suitable integrity in the stomach to achieve a sustained release of drug.. The rheological and gelation characteristics of solutions containing methylcellulose (2.0%) and sodium alginate (0.25-1.0%) were assessed for their suitability for administration to dysphagic patients. The gel strength and in vitro and in vivo release characteristics of gels formed by selected formulations were compared using paracetamol as a model drug.. Mixtures of 2.0% methylcellulose and 0.5% alginate containing 20% d-sorbitol were of suitable viscosity for ease of swallowing by dysphagic patients and formed gels at temperatures between ambient and body temperature allowing administration in liquid form and in situ gelation in the stomach. In vitro release of paracetamol from 2.0% methylcellulose/0.5% alginate gels was diffusion-controlled at pH 1.2 and 6.8. Measurement of plasma levels of paracetamol after oral administration to rats of a 2.0% methylcellulose/0.5% alginate formulation showed improved sustained release compared to that from 2.0% methylcellulose and 0.5% alginate solutions and from an aqueous solution of paracetamol.. Solutions of mixtures of methylcellulose and alginate in appropriate proportions are of suitable consistency for administration to dysphagic patients and form gels in situ with sustained release characteristics.

Topics: Administration, Oral; Alginates; Animals; Chemistry, Pharmaceutical; Deglutition Disorders; Delayed-Action Preparations; Diffusion; Dosage Forms; Drug Delivery Systems; Gastric Mucosa; Gels; Glucuronic Acid; Hexuronic Acids; Humans; Hydrogen-Ion Concentration; Male; Methylcellulose; Pectins; Rats; Rats, Wistar; Solutions; Temperature; Viscosity

Oral-sustained release gel formulations with suitable rheological properties have been proposed as a means of improving the compliance of dysphagic and geriatric patients who have difficulties with handling and swallowing oral dosage forms.. We have modified the rheological and release properties of thermally reversible methylcellulose solutions by admixture with pectin, the gelation of which is ion-responsive, with the aim of formulating an in situ gelling vehicle suitable for oral-sustained drug delivery.. Gels formed by solutions containing methylcellulose (1.0-2.0%) and pectin (0.5-2.0%) were assessed for suitable gel strength, and in vitro and in vivo release of paracetamol.. Addition of 1.5% pectin to a 2.0% methylcellulose formulation containing 20% d-sorbitol and calcium ions in complexed form increased the gel strength and provided a formulation with a suitable viscosity for ease of swallowing by dysphagic patients. Gels formed in situ after oral administration of this formulation retained their integrity in the rat stomach for sufficient time for sustained release to be achieved. In vitro release of paracetamol from methylcellulose, pectin, and methylcellulose/pectin gels was diffusion-controlled. Plasma levels of paracetamol after oral administration to rats (gastric pH 2.6 and 5.5) of a solution including 2.0% methylcellulose/1.5% pectin showed improved sustained release compared with that from both 2.0% methylcellulose and 1.5% pectin solutions.. The addition of suitable concentrations of pectin to methylcellulose solutions produces in situ gelling formulations with suitable viscosity for administration to dysphagic patients and improved sustained release characteristics.

Topics: Acetaminophen; Administration, Oral; Animals; Deglutition Disorders; Delayed-Action Preparations; Drug Compounding; Drug Delivery Systems; Gastric Mucosa; Gels; Humans; Male; Methylcellulose; Pectins; Rats; Rats, Wistar; Rheology; Viscosity