The In-Vitro Uptake of a Low Dose Drug (Riboflavine) by Some Adsorbents

An investigation was carried out of the in-vitro adsorption of a low-dose model drug (riboflavine) by three typzs of kaolin, attapulgite, magnesium trisilicate and a grade of magnesium aluminium silicate (veegum^R. The adsorption experiments were designed under conditions simulating in-vivo with respect to variations in pH values, volume of the adsorption medium, and the presence of electrolytes, a hydrophilic colloid and a surfactant. Under all conditions examined, riboflavine adsorption followed the sequence veegum attapulgite kaolin magnesium trisilicate

The presence of either veegum^R (1 g) or kaolin (4 g) in the medium reduced the level of drug in solution during dissolution rate testing of capsules. Desorption results suggest only partial release of the adsorbed drug. The results obtained emphasiz,e the strong uptake of a potent ionic drug by the various silicates commonly used in pharmacy.     

Effect of Attapulgite on the Bioavailability of a Model Low Dose Drug (Riboflavine) in Humans

Abstract

In human volunteers, both the rate and extent of urinary excretion of riboflavine were significantly reduced (p<0.05) when attapulgite was co-administered with the drug. About 50% reduction occurred in the cumulative amount excreted following the concurrent administration of 10 mg riboflavine in solution form and 2 g of regular attapulgite. The co-administration of the drug with a 30 ml dose of a commercial antidiarrheal suspension containing 10% activated attapulgite and 3% colloidal attapulgite produced a relatively lesser effect; the reduction in extent of absorption being 40%. No statistically-significant effect was found when the adsorbent was ingested 2 h prior to the drug. The observed reduction in drug bioavailability in the presence of attqapulgite to the significant uptake of the drug by the adsorbent.     

Oral Dosage Forms with Controlled Gastrointestinal Transit

Abstract

The present investigation concerns the development of new dosage forms which, after oral administration, exert an active influence on their gastrointestinal transit. The dosage forms release excipients which aim to increase the lenght of time the drug spends in the absorbing section of the duodenum and small intestine. A delayed gastrointestinal transit is intended to achieve a more complete and longer lasting absorption of drugs with a limited duration of absorption. The present study examined whether, by incorporating triethanolamine myristate (165 mg) as an excipient in tablets containing riboflavine (20 mg) as an example of a drug with limited absorption, the gastrointestinal transit of riboflavine could be delayed and hence its absorption improved. Five subjects took part in the in vivo studies and a pH-telemetering device (Heidelberg capsule) was used to determine gastric residence time.

The investigations showed that in 4 out of 5 subjects, the gastric residence time of the pH-telemetering capsule could be prolonged and the renal elimination of riboflavine increased The increase in renal elimination of riboflavine in the presence of triethanolamine myristate was statistically significant in the 4th urine collection period (0.05 > p> 0.0025).     

In Vitro Adsorption of Propranolol Hydrochloride by Various Antacids

The purpose of this study was to investigate by in vitro methods whether an interaction takes place between propranolol hydro-chloride and adsorbents when antacids are taken concomitantly with the beta-blocker or when excipients having adsorbent properties are present in formulations of the drug products containing propranolol hydrochloride.

Specific surface areas of magnesium trisilicate, magnesium oxide, magnesium hydroxide, dihydroxy aluminum sodium carbonate, magnesium carbonate and kaolin were calculated from nitrogen adsorption isotherm using single pint method and it was found. that magnesium trisilicate has the largest specific surface area.

The adsorption of propranolol hydrochloride to these adsorbents was investigated by in vitro methods. The adsorption isotherms were drawn and the adsorptive capacities of the adsorbents were calculated from the slopes. It was found that magnesium tri-silicate, magnesium hydroxide arid dihydroxy aluminum sodium carbonate possess the highest adsorptive capacities while kaolin and magnesium carbonate possess the lowest.

The results of the adsorption studies indicate that the concomitant use of propranolol hydrochloride and the above mentioned adsorbents could affect the bioavailability of the beta-blocker adversely.     

The Development of an Oral Controlled Release Pellets Formulation of Diethylpropion Hydrochloride

Abstract

In the present study, controlled release pellets of the anorexigenic, diethylpropion hydrochloride were formulated. Selected polymeric film coatings were applied to the drug-loaded non pareils and their effect on in vitro drug release from the multiple-units dosage form was examined. It was found that a combination of Eudragit^R RS, polyethylene glycol 200 and magnesium stearate produced a stable film coat that controlled drug release as desired. Dissolution data demonstrated that this formulation displayed predictable and reproducible drug release characteristics.     

Effect of Particle Size and Excipients on the Dissolution Rate of Metronidazole from Solid Dosage Forms: II

Abstract

In-vitro dissolution tests were carried out with tablets prepared from different particle size ranges of metronidazole. Influence of tablet binding agents (Methylcellulose, polyvinyl pyrrolidone - (PVP), potato starch and gelatin) on the drug release were investigated under similar conditions. Comprimates containing PVP and drug with particle size 1.75 μm (in lactose mixture) gave optimum results. These findings may open new ways of formulating a metronidazole tablet exhibiting improved drug - liberation, subsequently with a better bioavailability than the KUON^R-Tablet manufactured in Hungary.     

Effect of Some Excipjents and Compression Pressure on the Adhesion of Aqueous-Based Hydroxypropyl Methylcellulose Film Coatings to Tablet Surface

Abstract

The adhesion between aqueous-based hydroxypropyl methylcellulose (HPMC) films and tablet surface was evaluated using a Lloyd LRX materials testing machine. Special attention was paid to the effects of compression pressure and the excipients (microcrystalline cellulose, lactose and a commercial combination of lactose and cellulose (Cellactose^R)) on the adhesion properties of the film.

The adhesion of HPMC films was the lowest for the tablets containing lactose as a diluent and the highest for the tablets containing microcrystalline cellulose. The adhesion to Cellactose^R-based tablets increased with increasing compression pressure. With microcrystalline cellulose (MCC) and lactose, the effect of compression pressure on film adhesion was not so clear. The increase in concentration of a hydrophopic lubricant, magnesium stearate, decreased the adhesion between the films and tablets cores. The greatest decrease was observed with the MCC tablets.

Furthermore the results showed that, the film coating increased clearly the mechanical strength of the tablets, depending on the excipient, the compression pressure and amount of magnesium stearate.     

Adsorption Characteristics of Norfloxacin to Pharmaceutical Additives

Abstract

Norfloxacin is a very potent drug, adsorption of even a few milligrams of this drug may account for a significant fraction of total dose, hence, adsorption effect might be of great significance. The results of in vitro adsorption studies of norfloxacin to different pharmaceutical additives are plotted on the basis of Langmuir Equation. The linear nature of the adsorption isotherms shows that the adsorption process is due to monomolecular layer. Adsorption constants were calculated to determine the binding capacity of this drug to various additives. The adsorbents with their decreasing binding capacity are as follows:

Activated charcoal (33.0 × 10^?3) > Bentonite (17.0 × 10^?3) > Kaolin (9.5 × 10^?3) > Methyl cellulose (8.6 × 10^?3) > Potato starch (7.4 × 10^?3) > Talc (6.0 × 10^?3)

The mechanism of adsorption has been discussed in light of physical characteristics of the adsorbents.     

In Vitro Adsorption-Desorption of Papaverine Hydrochloride by Montmorillonite

Abstract

In an attempt to obtain the basic data necessary in research into the possible use of papaverine in sustained action formulas in the form of complexes with Montmorillonite, the “in vitro” adsorption and desorption of the drug as a function of different factor was studied.

The study of the interaction and adsorption mechanisms was carried out by adsorption isotherms, X-ray diffraction and I.R. spectroscopy.

The adsorption of papaverine by Montmorillonite increases with the rise in pH of the solution, within the pH range studied (2-4) in agreement with the solubility of the compound. According to the isotherms, adsorption increases with the concentration of the solution up to 79.16 mEq/100 g (very close to the exchange capacity of the clay). The data fulfill Langmuir's equation, implying a chemical adsorption mechanism.

The results of the X-ray diffraction and I.R. spectroscopy studies confirm the intercalation of the organic cation into the interlayer space of montmorillonite, forming a complex of defined spacing (17.66 Å (DL = 8.06 Å)). The studies revealed that cation exchange is the mechanism responsible for this interaction.

The “in vitro” desorption studies showed that the amount of papaverine desorbed from the complex depends on the pH of the solution, on its ionic strength, on the presence of free drug and on the elimination rate of the desorbed complex; in all cases, desorption was seen to be very low.

In general, release of the drug follows a single first order kinetic process with a rapid initial desorption of the drug.     

Development of novel amisulpride-loaded solid self-nanoemulsifying tablets: preparation and pharmacokinetic evaluation in rabbits

Objective: The current investigation is focused on the formulation and in vivo evaluation of optimized solid self-nanoemulsifying drug delivery systems (S-SNEDDS) of amisulpride (AMS) for improving its oral dissolution and bioavailability.

Methods: Liquid SNEDDS (L-SNEDDS) composed of Capryol? 90 (oil), Cremophor^® RH40 (surfactant), and Transcutol^® HP (co-surfactant) were transformed to solid systems via physical adsorption onto magnesium aluminometasilicate (Neusilin US2). Micromeretic studies and solid-state characterization of formulated S-SNEDDS were carried out, followed by tableting, tablet evaluation, and pharmacokinetic studies in rabbits.

Results: Micromeretic properties and solid-state characterization proved satisfactory flow properties with AMS present in a completely amorphous state. Formulated self-nanoemulsifying tablets revealed significant improvement in AMS dissolution compared with either directly compressed or commercial AMS tablets. In vivo pharmacokinetic study in rabbits emphasized significant improvements in t_max, AUC_(0–12), and AUC_(0–∞) at p?<?.05 with 1.26-folds improvement in relative bioavailability from the optimized self-nanoemulsifying tablets compared with the commercial product.

Conclusions: S-SNEDDS can be a very useful approach for providing patient acceptable dosage forms with improved oral dissolution and biovailability.     

A Study on the Manufacture and in Vitro Dissolution of Terbutaline Sulfate Microcapsules and their Tablets

Abstract

Microcapsules of terbutaline sulfate with cellulose acetate butyrate and ethylcellulose were prepared using an emulsion-solvent evaporation technique. The in vitro dissolution of terbutaline sulfate was studied using the USP rotating basket method. As the polymer to drug ratio increased, the microcapsule size distribution shifted to the smaller size and the release of terbutaline sulfate decreased. The release of terbutaline sulfate was independent of the dissolution medium pH for both polymers. The release kinetics from the microcapsules was dependent on the polymer type and polymer to drug ratio. The release of terbutaline sulfate from cellulose acetate butyrate and ethylcellulose microcapsules formulated with a 1:1 polymer to drug ratio was complex and could not be differentiated between the square-root of time and first-order release models. However, the square-root of time model was followed by microcapsules formulated with a 2:1 or a 3:1 cellulose acetate butyrate to drug ratio. When the ethylcellulose to drug ratio was increased to 2:1 the square-root of time model was followed. At an ethylcellulose to drug ratio of 3:1 the release kinetics could not be differentiated between the Hixon-Crowell and first-order release models. The T50% from ethylcellulose microcapsules was decreased when the microcapsules were compressed into tablets with the addition of Avicel^R/Emcompress^R (2:1) or Avicel^R.     

Binder effectiveness for beads with high drug levels

Abstract

Previous reports from these laboratories showed that microcrystalline cellulose (Avicel^R MCC, PH-101) formulations with low and medium drug levels (10 and 50%) produced very uniform beads whereas formulations containing MCC with high drug levels (80%) were difficult to process without special treatment or required the incorporation of alternate excipients. In this study, several binders, at a 2% level, specifically: Carbomer (Carbopol^R 934-P), Sodium carboxymethylcellulose (CMC 7MF), Hydroxypropylcellulose (Klucel^R HXF), Methylcellulose (Methocel^R K-15). Povidone, USP (PVP K29-32) and Pregelatinized starch NF (Starch 1500^R), were evaluated to determine whether they might impart advantages in processing and whether any differences in dissolution behavior would result. Spheres containing 80% anhydrous theophylline, the binders and MCC were manufactured by the extrusion/marumerization technique. In general, beads containing high drug levels produced with these binders are suitable for further processing (coating). Processing ease, bead shape, and bead hardness (friability) varied with the choice of binder. Beads with carbomer, hydroxypropylcellulose, and methylcellulose remained intact during dissolution testing; beads with starch, carboxymethylcellulose, PVP, and the control did not.     

THe Incorporation and in Vitro Release Profiles of Liquid,Deliquescent or Unstable Drugs with Fusible Excipients in Hard Gelatin Capsules

Abstract

The in vitro release profiles of four liquid or deliquescent model drugs incorporated in various Gelucire^R excipients were examined. In every case, it was possible to obtain release of the active substance as rapidly as with the equivalent commercial soft gelatine capsules tested. Gelucire^R grades with high HLB values (despite having high melting points) were found to be the most favorable. Release patterns could be related to the behaviour of the Gelucire^R bases in the gastric fluid

Drug-excipient ratio played a prominent role, which differed when hydrophilic or hydrophobic Gelucire^R types were used. Storage of the capsule formulations for more than two years did not usually change the drug release profiles significantly, but chloral hydrate capsules could not be stocked for more than a few months     

In vitro and in vivo investigation of taste-masking effectiveness of Eudragit E PO as drug particle coating agent in orally disintegrating tablets

Abstract

Context: Considering that bitter taste of drugs incorporated in orally disintegrating tablets (ODTs) can be the main reason for avoiding drug therapy, it is of the utmost importance to achieve successful taste-masking. The evaluation of taste-masking effectiveness is still a major challenge.

Objective: The objective of this study was to mask bitter taste of the selected model drugs by drug particle coating with Eudragit^® E PO, as well as to evaluate taste-masking effectiveness of prepared ODTs using compendial dissolution testing, dissolution in the small-volume shake-flask assembly and trained human taste panel.

Materials and methods: Model drugs were coated in fluidized bed. Disintequik? ODT was used as a novel co-processed excipient for ODT preparation. Selected formulations were investigated in vitro and in vivo using techniques for taste-masking assessment.

Results and discussion: Significantly slower drug dissolution was observed from tablets with coated drug particles during the first 3?min of investigation. Results of in vivo taste-masking assessment demonstrated significant improvement in drug bitterness suppression in formulations with coated drug. Strong correlation between the results of drug dissolution in the small-volume shake-flask assembly and in vivo evaluation data was established (R?≥?0.970).

Conclusion: Drug particle coating with Eudragit^® E PO can be a suitable approach for bitter taste-masking. Strong correlation between in vivo and in vitro results implicate that small-volume dissolution method may be used as surrogate for human panel taste-masking assessment, in the case of physical taste-masking approach application.     

Adsorptive capacity of spray-dried pH-treated bentonite and kaolin powders for ammonium removal

The effectiveness of ammonium (NH₄⁺) adsorption was investigated, using spray-dried, pH-treated bentonite, and kaolin as adsorbents. Each powder's adsorption capacity towards NH₄⁺ was examined after up to 120 min of sample exposure, and results were compared. The zeta potential values for bentonite samples were between ?1.1 and ?19.4 mV, while for kaolin samples, they were between ?35.7 and ?40.9 mV (pH range examined was 2–10). The adsorption isotherm for bentonite showed a fit with the Langmuir model. The pH 10-treated bentonite and as-received bentonite (dispersed as pH 10 in distilled water) showed the highest adsorption capacity towards NH₄⁺. Meanwhile, for kaolin, the adsorption capacity was low and observed only at low NH₄⁺ concentration (100 mg/L and 200 mg/L), with pH 10-treated kaolin showed the highest adsorption capacity.     

Adsorption of Some 1. 4-Benzodiazepines on Insoluble Tablet Excipients and Charcoal

Abstract

The adsorption of five widely used 1. 4-benzodiazepines on talc, calcium phosphate, magnesium stearate, microcrystalline celluloses, ethyl cellulose and starch was studied. Adsorption of these compounds on charcoal was also investigated for comparison. Diazepam was found not to be adsorbed on talc, calcium phosphate and magnesium stearate. A relatively low adsorption of the drug by cellulose and starch was measured. The amount of diazepam adsorbed per unit weight of ethyl cellulose was high in water and in phosphate buffer, while no adsorption could be measured in 0.1 N HCL. The drug interact with ethyl cellulose at higher concentrations (100-180 mcg/ml). The UV and IR of the reactants and products were studied.

The adsorption of nordiazepam, nitrazepam, flunitrazepam and chlordiazepoxide onto ethyl cellulose and charcoal from their aqueous solutions was also studied. Diazepam and nordiazepam showed the highest adsorption on ethyl cellulose. The desorption of benzodiazepines from ethyl cellulose in 0.1 N HC1 was at the following decreasing rate: flunitrazepam, chlordiazepoxide, nitrazepam, diazepam, nordiazepam.     

Influence of the Drug and Ezcipient Solubility on the Antibiotic Release from Polymethacrylic Implants

Abstract

Polymethacrylic implants were prepared by use the monomer (Kallocryl^R) and a polymerization extrusion technique. The antibiotics used were gentamicine, streptomycine and chloramphenicol. The excipients used were amino acids with various solubilities and titan dioxyde as an inert and insoluble matrix filler. The drug release examined in vitro by use a modified pitcher/half change method was dependent on the mechanical strength of the matrix, the concentration and the solubility of the amino acid used and the drug concentration and solubility.

The water inflow into the matrix was of effect on the volume of pores and may be influenced by the drug and excipient particle size and solubility.

There was a relationship between the time dependent volume of pores in the matrix and the amount of drugs released from the implants.     

THE PROPER USE OF WATER LIQUID PARTICLE COUNTERS

ABSTRACT

In the present work the removal of iron, present as impurity in a kaolin of industrial interest, was performed. An effective iron reduction using microbial mixed cultures was attained (up to 81%) while a significant iron reduction in the presence of single microbial cultures was achieved (up to 37%).

The active microorganisms belong to the genera Bacillus and Agrobacter. The enzymatic and un-enzymatic iron reduction was evaluated.

Finally the molasses as carbon source for heterotrophic bacteria were succesfully tested.     

Bioactive Polymers 62. A Novel Macromolecular Drug Based on 5-Acetylamino-2-Sulfamoyl-1,3,4 Thiodiazole

Abstract

The condensation reaction of 5-acetylamino-2-sulfamoyl-1,3,4 thiodiazole (acetazolamide) on the poly(acrylic acid-co-styrene) copolymer was studied, with a view to obtaining a retard drug. Coupling was performed in a THF medium in the presence of dicyclohexylcarbodiimide as activator. The diuretic effect of the newly obtained drug was checked in rats.     

Adsorption of Gelatin at Solid-liquid Interfaces

Abstract

The adsorption of acid processed gelatin on to silica has been studied from the aqueous solution of gelatin at room temperature (25 °C). Various adsorption and kinetic parameters have been evaluated, such as the adsorption coefficient, rate constants for the adsorption and desorption, and diffusion constants and the effects of different factors on the extent of adsorption have been studied such as the pH of the solution, presence of inorganic salts and solvents, and temperature of the reaction medium.