Biomedical subjects

D J Chetty

Publications and source records attributed to D J Chetty.

9 recordsLinked to original sources

PubMed2006

Statistical optimisation of the mucoadhesivity and characterisation of multipolymeric propranolol matrices for buccal therapy.

A Box-Behnken experimental design was employed to optimise a polymeric blend for the preparation of propranolol HCl matrices with maximum mucoadhesivity and was thereafter modified for achieving controlled drug release. The quantitative effects of the polymers used i.e. poly(acrylic acid) (PAA) and poly(vinyl pyrrolidone) (PVP) on mucoadhesion could be predicted using polynomial equations. A formulation of 20% PAA, 20% CMC and 20% PVP was identified for maximising mucoadhesivity and obtaining a controlled drug release profile. Reproducibility of the optimal formulation in terms of mucoadhesivity and controlled drug release was confirmed. The optimal formulation was characterised in terms of mucoadhesivity, release kinetics, swelling/erosion, hydration dynamics and surface pH. From the model fitting analyses, drug release was found to be diffusion, polymeric relaxation and erosion based with the former two being more dominant over erosion. This was in agreement with the erosion and swelling studies which showed swelling and erosion occurring in the tablet matrix. Textural profiling showed initial rapid hydration, which could be beneficial for enhanced mucoadhesivity. Surface pH of the multipolymeric matrices was similar to salivary pH and did not show extremes in changes over the test period. The optimal preparation of multipolymeric propranolol matrices identified in this study shows potential for buccal administration.

Acrylic Resins↗

PubMed2006

Enhancing drug incorporation into tetracycline-loaded chitosan microspheres for periodontal therapy.

PURPOSE: To identify optimal formulation parameters for enhancing the incorporation of tetracycline hydrochloride into chitosan microspheres for periodontal therapy. METHODS: Tetracycline-loaded chitosan microspheres were prepared by ionotropic gelation. Various formulation parameters (salt form of drug, aqueous phase pH, anion structure, inorganic salts and electrolytes, preparation method) were investigated for their influence on drug incorporation efficiency. Microspheres were assessed in terms of drug entrapment and content, microsphere recovery, particle size and morphology. RESULTS: Although drug incorporation efficiency was increased marginally, the use of a dihydrate form of the drug was not considered feasible due to the lowered microsphere recovery and higher costs. A decrease in the aqueous pH from 9 to 6 enhanced drug incorporation efficiency without an adverse effect on microsphere morphology. The use of inorganic salts/electrolytes and other approaches of microsphere preparation did not significantly enhance drug incorporation efficiency and these approaches also adversely affected microsphere morphology. The ionotropic preparation method in terms of the drug loading technique significantly affected drug incorporation efficiencies. CONCLUSIONS: This study has shown that formulation variables can be exploited in order to enhance the incorporation of a water soluble drug into chitosan microspheres using the ionotropic gelation technique. Based on a comparison of all results obtained with the different approaches, the modification of the aqueous phase to pH 6 was identified as the most feasible approach.

Anions↗

PubMed2005

Optimisation and characterisation of bioadhesive controlled release tetracycline microspheres.

A Box-Behnken experimental design was employed to statistically optimise the formulation parameters of a tetracycline microsphere preparation for maximum bioadhesivity and controlled drug release. The quantitative effect of the formulation parameters at different levels on bioadhesion and drug release could be predicted using polynomial equations. A formulation comprising of 3% (w/w) chitosan, 10% (w/w) tetracycline HCl and 9% (w/v) tripolyphosphate was identified for maximising bioadhesivity and obtaining controlled drug release. The optimal microsphere preparation was subsequently characterised in terms of hydration dynamics, release kinetics, antimicrobial activity, thermal properties, morphology and surface pH. Kinetic models revealed that drug release followed Fickian diffusion while textural analysis showed minimal hydration over the test period. Antimicrobial studies showed that the drug concentrations in the in vitro release samples were above the minimum concentration of drug required for inhibition of Staphylococcus aureus growth. Thermal analyses showed a possible interaction between the drug and polymer. Scanning electron microscopy confirmed the integrity of the microspheres and identified the morphological changes following drug release. Surface pH of the microspheres was similar to salivary pH and did not show extremes in changes over the test period.

Adhesiveness↗

PubMed2001

Characterization of captopril sublingual permeation: determination of preferred routes and mechanisms.

Although sublingual captopril has been used clinically to treat hypertensive emergencies, a mechanistic understanding of sublingual permeation will facilitate the optimization of drug delivery. A correlation of sublingual steady-state flux with donor captopril concentration in a porcine model showed the absence of saturability and suggested a passive diffusion permeation mechanism. A simultaneous evaluation of permeability and partition coefficient demonstrated that the paracellular route is the predominant pathway for sublingual permeation. The enhancement factors of specific ion permeabilities in the presence of tight junction perturbants indicated that although the paracellular pathway is preferred by the ionized species of captopril, the lipophilic transcellular pathway is preferred by the neutral, un-ionized species.

Animals↗

PubMed1999

A mechanistic analysis to characterize oramucosal permeation properties.

The hypotheses of this study are that the permeation of ionizable molecules follows the pH-partition theory, that the preferred transport pathway for penetrants depends on their charge status and that transport resistance is related to the membrane-coating granules (MCG). Transcellular resistance is believed to be proportional to the volume of MCG in the intracellular space while paracellular resistance is believed to result from the extrusion of the lipid contents of the MCG into the intercellular space. Nicotine, an ionizable model compound with two pK(a) values (3.4 and 8.2), was chosen as a molecular probe to investigate the pH-partition theory on permeation through porcine oramucosae, to characterize the differences in permeability among various oramucosae, and to explore the preferred transport pathways of each nicotine species through oramucosae. The pH-partition theory was proved from the observations that permeability, partition coefficient and diffusivity of nicotine varied as a function of pH. The keratinized gingiva was found to have greater permeability than the non-keratinized buccal and sublingual mucosae. The neutral nicotine species had a higher permeability than the ionized species due to its higher partition coefficient and diffusivity. A mechanistic analysis (permeability ratio-pH profile) was conducted to determine the preferred transport pathway of each nicotine species. The permeability of neutral nicotine was found to be proportional to the occupied volume of MCG in the intracellular space. This indicates that the preferred transport pathway for neutral nicotine is transcellular. As the solution pH was decreased, and a greater fraction of nicotine became protonated, the transport of hydrophilic, charged nicotine species along the intercellular pathway was preferred.

Animals↗

PubMed1998

Novel methods of insulin delivery: an update.

Conventional insulin therapies involve multiple daily subcutaneous injections. However, the resultant disposition of insulin and blood glucose differs considerably from that following the physiological secretion of pancreatic insulin. A variety of alternative routes/methods have been investigated to improve systemic insulin delivery. Peroral and nasal insulin administration have demonstrated good potential for the treatment of diabetes. Facilitated transdermal delivery has also enjoyed success in promoting the systemic delivery of insulin. In addition, pulmonary, buccal, and ocular insulin administration have been shown to decrease serum glucose concentrations. Other methods that have been investigated for their potential in systemic insulin delivery include rectal, vaginal, and uterine routes.

Administration, Oral↗

PubMed1997

Biomembrane permeation of nicotine: mechanistic studies with porcine mucosae and skin.

In the present study, the permeation and partitioning of nicotine as a function of pH was investigated with various regions of skin and absorptive mucosae that were freshly excised from domestic pigs. As an ionizable compound (pKa values of 3.04 and 7.84), nicotine in solutions of different pH values provides a model for determining the influence of the charge status of a molecule on permeation. The permeation of nicotine across porcine mucosae and skin followed zero-order kinetics. The rate of permeation was dependent on donor solution pH and increased exponentially as the pH increased. With an exception of the nasal mucosa, which showed similar permeabilities for all species of nicotine, the permeability of nicotine across various skin and mucosal specimens was significantly higher (p < 0.001) for the un-ionized species (NN) than for the ionized species (NNH+, NH+NH+). It was also seen that un-ionized nicotine molecules were more permeable through absorptive mucosae (nasal, buccal, sublingual, and gingival) than through skin (abdominal, dorsal, thigh, and ear pinna). Partition studies were performed and the results further confirmed that biomembrane permeation of nicotine follows the pH-partition theory.

Animals↗

PubMedDate not supplied

In vitro characterization of a controlled-release chlorpheniramine maleate delivery system prepared by the air-suspension technique.

Non-pareil cores were spray-coated with a chlorpheniramine maleate (an alkylamine antihistamine) layer and a Eudragit NE30D overcoat in a Wurster air-suspension apparatus. In vitro dissolution studies demonstrated that drug release was a function of polymer membrane thickness. Polyethylene glycol 6000, as a hydrophillic additive, increased the in vitro release of chlorpheniramine maleate from the pellets. Pellets coated with 8.30% Eudragit NE30D, 0.50% talc and 1.00% polyethylene glycol 6000 were found to display desirable controlled release characteristics for chlorpheniramine maleate over the 8-h testing period, which were also comparable with that of Dykatuss capsules. The controlled release pellets exhibited first-order release characteristics for chlorpheniramine maleate. Reproducibility of the manufacturing conditions employed in the study were confirmed thus ensuring reproducibility of drug release characteristics between batches of chlorpheniramine maleate pellets. Drug release from the pellets was shown to be independent of the dissolution method and medium used. Pellets displayed no significant change in drug release characteristics relative to the initial drug release data when stored for 12 weeks at room temperature (20 +/- 2 degrees C) and for 8 weeks at a low temperature (5 +/- 1 degrees C). However, pellets stored at 37 degrees C with 80% relative humidity and at 40 +/- 2 degrees C showed a slower in vitro drug release after 8-week storage and therefore failed to maintain their initial drug release profile.

Capsules↗

PubMedDate not supplied

Microencapsulated Eudragit RS30D-coated controlled-release pellets: the influence of dissolution variables and topographical evaluation.

The air suspension technique was employed to prepare Eudragit RS30D-coated controlled-release pellets of salbutamol. Drug release in dissolution studies can be dependent on the dissolution method and medium used. Thus, the aim of this study was to investigate the influence of various dissolution methods and dissolution medium pH values on drug release from a batch of pellets which displayed controlled drug-release characteristics over an 8-h period in deionized water using the rotating basket method. In vitro testing using the official USP XXII (rotating basket and rotating paddle) and non-official (rotating bottle) methods showed drug release to be independent of the method used. The prepared pellets displayed pH-dependent drug-release characteristics when tested in hydrochloric acid (pH 1.5), phosphate buffer (pH 6.8) and deionized water (pH 7.2). Also, in vitro testing, which exposed the pellets to a changing pH gradient that simulated the gastrointestinal pH conditions following oral administration, was used to confirm the drug-release characteristics. The results showed controlled-release characteristics to be maintained, with the drug being released over an 8-h period. Scanning electron microscopic evaluation proved useful in the elucidation of the physical characteristics of the controlled-release pellets as well as in the identification of a possible mode of drug transfer into the dissolution medium.

Acrylic Resins↗