ABSTRACT
The objective of this study was to evaluate the effect of intensity, mode, and duration of ultrasound application on the transport of three nonsteroidal anti-inflammatory drugs (NSAIDs) across cellulose membrane and rabbit-skin. Ibuprofen, piroxicam and diclofenac sodium were used as the model drugs. Studies were performed in vitro using a modified Franz diffusion assembly adapted to a therapeutic ultrasound transducer. Ultrasound had a significant and positive effect on the transport of the model NSAIDs across cellulose and rabbit skin membranes. Increasing ultrasound intensity from 0.5 to 3.0 W/cm2 led to a proportional increase in drug transport. Continuous ultrasound mode was more effective in enhancing drug transport than the pulsed mode. Diclofenac sodium had the least flux and permeability coefficient. This was attributed to its comparatively lower pKa value that renders the drug more ionizable in the buffer solution, consequently reducing its selective penetration through the membranes. This study demonstrated the therapeutic potential of ultrasound in transdermal delivery of NSAIDs and the synergistic effect of temperature and ultrasound operational parameters on drug transport.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Phonophoresis , Skin Absorption/radiation effects , Animals , Cellulose , Diclofenac/administration & dosage , Diclofenac/pharmacokinetics , Diffusion , Ibuprofen/administration & dosage , Ibuprofen/pharmacokinetics , In Vitro Techniques , Membranes, Artificial , Pharmaceutical Vehicles , Piroxicam/administration & dosage , Piroxicam/pharmacokinetics , Rabbits , UltrasonicsABSTRACT
Salbutamol sulfate beads were prepared using anionic and cationic polysaccharides, Gelrite and chitosan, respectively. Alginate beads were also prepared for comparison. The mean diameter, porosity, and drug content of the beads were determined. The beads were examined by scanning electron microscopy (SEM), DSC, and x-ray diffraction. The drug release from the beads was studied in 0.1 N HCl (pH 1.2), distilled water, and phosphate buffer (pH 7.4). The physical examination of the beads indicated the presence of drug crystals with no interaction between the drug and polymers. The drug release was dependent on the ionic properties of the polymers and the pH of the release media. In acidic pH, chitosan beads showed a rapid drug release, whereas a sustained drug release was obtained from Gelrite beads. In contrast, the drug release in phosphate buffer was rapid from Gelrite, and chitosan showed a sustained drug release. The results of drug release from Gelrite were comparable to that from alginate beads. Gelrite is recommended as an anionic polysaccharide for sustained-release preparations.
Subject(s)
Albuterol/administration & dosage , Polysaccharides , Albuterol/chemistry , Albuterol/pharmacokinetics , Calorimetry, Differential Scanning , Chemical Phenomena , Chemistry, Physical , Chitin/analogs & derivatives , Chitin/chemistry , Chitosan , Delayed-Action Preparations , Drug Carriers , Humans , Hydrogen-Ion Concentration , In Vitro Techniques , Ions , Microscopy, Electron, Scanning , Particle Size , Polysaccharides/chemistry , Polysaccharides, Bacterial/chemistry , X-Ray DiffractionABSTRACT
Azapropazone was encapsulated with pectin-rutin mixture using the fluidized bed technique. The encapsulated particles showed higher dissolution rate and bioavailability but lower ulcerogenic activity as compared with the drug alone.
Subject(s)
Apazone/pharmacokinetics , Drug Compounding/methods , Pectins/chemistry , Rutin/chemistry , Animals , Apazone/administration & dosage , Apazone/toxicity , Biological Availability , Male , Particle Size , Rats , Stomach Ulcer/chemically inducedABSTRACT
Acidic and basic nonsteroidal anti-inflammatory drugs were encapsulated with cellulose derivatives having different functional groups, acidic (carboxymethyl cellulose), basic (chitosan), and neutral (hydroxypropylmethyl cellulose). The properties of the microcapsules were studied and the interaction of the drugs with chitosan was assessed.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Drug Compounding/methods , Carboxymethylcellulose Sodium , Chemical Phenomena , Chemistry , Chitin/analogs & derivatives , Chitosan , Glafenine , Hypromellose Derivatives , Methylcellulose/analogs & derivatives , OxyphenbutazoneABSTRACT
The bioavailability and gastric ulcerogenic activity of oxyphenbutazone and glafenine (acidic and basic nonsteroidal anti-inflammatory drugs), coated with different cellulose derivatives were assessed in albino rats. The cellulose derivatives chosen have different functional groups, acidic (carboxymethyl cellulose), basic (chitosan) and neutral (hydroxypropylmethyl cellulose). The bioavailability was dependent on the drug and polymers. Generally, all the cellulose derivatives chosen decreased the gastric ulcerogenic activity of the drugs studied.
Subject(s)
Glafenine/administration & dosage , Oxyphenbutazone/administration & dosage , Stomach Ulcer/chemically induced , ortho-Aminobenzoates/administration & dosage , Animals , Biological Availability , Capsules/adverse effects , Carboxymethylcellulose Sodium , Chitin/analogs & derivatives , Chitosan , Glafenine/adverse effects , Glafenine/pharmacokinetics , Hypromellose Derivatives , Male , Methylcellulose/analogs & derivatives , Oxyphenbutazone/adverse effects , Oxyphenbutazone/pharmacokinetics , Rats , Time FactorsABSTRACT
Different classes of nonsteroidal anti-inflammatory drugs, NSAIDs, were separately coated with cationic (E) and anionic (L) Eudragit using the fluidized bed technique. The bioavailability and ulcerogenic activity of coated and uncoated drugs were assessed in rats. The cationic coat decreased the ulcerogenic activity in all classes of NSAIDs and increased the bioavailability only in acidic and enolic ones. The anionic coat, however, increased the bioavailability in basic NSAIDs.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Stomach Ulcer/chemically induced , Animals , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Biological Availability , Capsules , Male , RatsABSTRACT
Nonsteroidal anti-inflammatory drugs, NSAIDs, were encapsulated with cationic and anionic Eudragit polymers. The properties of the microcapsules were studied. The interactions, if any, between the polymers and NSAIDs were also investigated.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Capsules , Hydrogen-Ion Concentration , SolubilityABSTRACT
The adsorption of the urinary tract analgesic, phenazopyridine hydrochloride (PN . HCl), on some silicates as pharmaceutical adjuvants was studied. From Langmuir adsorption isotherms the adsorption capacities were determined. The results revealed that the adsorption capacities of veegum and bentonite were comparatively higher than kieselguhr, talc and kaolin. High adsorption capacities of veegum and bentonite were also obtained at pH values ranging between 2 to 4 simulating those of the stomach juice. Bioavailability studies proved that bentonite decreased the rate as well as extent of absorption of PN . HCl from rats.
Subject(s)
Adjuvants, Pharmaceutic , Aminopyridines , Phenazopyridine , Absorption , Biological Availability , Chemistry, Pharmaceutical , Colorimetry , Hydrogen-Ion Concentration , Solubility , ThermodynamicsSubject(s)
Aminopyridines/metabolism , Phenazopyridine/metabolism , Adsorption , Adult , Bentonite , Biological Availability , Hardness , Humans , Male , Phenazopyridine/administration & dosage , Solubility , Tablets , Time FactorsABSTRACT
Naturally occurring tetracycline antibiotics were tested for active transport in a standard everted rat gut preparation. The ratio of drug concentrations between serosal and mucosal solutions was measured as well as the rate of transport at different mucosal concentrations. Although a ratio of near unity was demonstrated by all the antibiotics, indicating passive transport, the rate of transport was linear only at low concentrations. A mechanism of more than simple diffusion was suggested. A carrier with limited capacity present in the intestinal tissue might be responsible for the transport of these antibiotics.
Subject(s)
Intestinal Absorption , Tetracyclines/metabolism , Animals , Biological Transport, Active , In Vitro Techniques , Rats , Solubility , Surface Tension , Time FactorsABSTRACT
Alpha tocopherol (vitamin E) deficiency has been shown to cause changes in membrane structure. The present study relates alpha tocopherol deficiency with increased rates of transport and absorption of passively absorbed drugs. The pharmacokinetics of barbital in alpha tocopherol-deficient and control rats was studied. The barbital absorption rate constant in deficient animals increased compared to control values. This findings indicates that alpha tocopherol deficiency affects the intestinal membrane structure. This finding was confirmed by studying the intestinal transport of phenolsulfonphthalein, barbital, and salicylate using the everted gut technique. Phenolsulfonphthalein was transported more rapidly through the alpha tocopherol-deficient gut, but this difference was not significant after 30 min, probably due to membrane decomposition. Barbital, which is more lipid soluble and less dependent on changes in pore volume and size, was transported more rapidly through the deficient gut during the entire experiment. The transport rate of salicylate was not altered by the deficiency state. This result was expected since the drug is normally rapidly transported; therefore, comparatively small changes in permeability such as those induced by alpha tocopherol deficiency would be masked. After the oral administration of phenolsulfonphthalein to intact animals, a significantly higher amount of drug was recovered in the urine of the deficient group.
