Compatibility of chewing gum excipients with the amino acid L-cysteine and stability of the active substance in directly compressed chewing gum formulation.

Using L-cysteine chewing gum to eliminate carcinogenic acetaldehyde in the mouth during smoking has recently been introduced. Besides its efficacy, optimal properties of the gum include stability of the formulation. However, only a limited number of studies exist on the compatibility of chewing gum excipients and stability of gum formulations.

Formulation and in-vivo evaluation of L-cysteine chewing gums for binding carcinogenic acetaldehyde in the saliva during smoking.

Cigarette smoke contains toxic amounts of acetaldehyde that dissolves in saliva, posing a significant risk of developing oral, laryngeal and pharyngeal carcinomas. L-cysteine, a non-essential amino acid, can react covalently with carcinogenic acetaldehyde to form a stable, non-toxic 2-methylthiazolidine-4-carboxylic acid. The main aim of this study was to find out whether it is possible to develop a chewing gum formulation that would contain cysteine in amounts sufficient to bind all the acetaldehyde dissolved in saliva during the smoking of one cigarette.

Neutron activation based gamma scintigraphic evaluation of enteric-coated capsules for local treatment in colon.

The fate of two colon-specific formulations developed in our previous study was investigated using a gamma scintigraphic imaging method. The formulations contained paracetamol and samarium oxide (Sm2O3) and either microcrystalline cellulose (MCC) or hypromellose (HPMC K4M) as diluent and were coated with Eudragit S polymer. The gamma scintigraphic evaluation proved that the products remained intact in the stomach and the upper gastrointestinal tract.

Anthranoid laxatives influence the absorption of poorly permeable drugs in human intestinal cell culture model (Caco-2).

Interactions between widely used anthranoid laxatives and other simultaneously administered drugs are not known. In this paper, the influence of rhein, danthron, sennidins A/B, sennosides A/B, and senna leaf infusion was investigated on the permeability of furosemide, ketoprofen, paracetamol, propranolol, verapamil, digoxin, and Rhodamine 123 across Caco-2 monolayers. The effects on monolayer integrity ([(14)C]mannitol permeability, TEER) were also determined.

Level A in vitro-in vivo correlation (IVIVC) model with Bayesian approach to formulation series.

In vitro-in vivo correlation (IVIVC) models for formulation series are useful in drug development, but the current models are limited by their inability to include data variability in the predictions. Our goal was to develop a level A IVIVC model that provides predictions with probabilities. The Bayesian approach was used to describe uncertainty related to the model and the data.

Eliminating carcinogenic acetaldehyde by cysteine from saliva during smoking.

Tobacco smoking is one of the strongest risk factors not only for lung cancer but also for cancers of the upper gastrointestinal tract. Acetaldehyde has been shown to dissolve into the saliva during smoking and to be a local carcinogen in the human upper digestive tract. Cysteine can bind to acetaldehyde and eliminate its toxicity.

Pellet manufacturing by extrusion-spheronization using process analytical technology.

The aim of this study was to investigate the phase transitions occurring in nitrofurantoin and theophylline formulations during pelletization by extrusion-spheronization. An at-line process analytical technology (PAT) approach was used to increase the understanding of the solid-state behavior of the active pharmaceutical ingredients (APIs) during pelletization. Raman spectroscopy, near-infrared (NIR) spectroscopy, and X-ray powder diffraction (XRPD) were used in the characterization of polymorphic changes during the process.

Are chitosan formulations mucoadhesive in the human small intestine? An evaluation based on gamma scintigraphy.

Rapid passage through the proximal intestine can result in the low bioavailability of a drug substance with site-specific absorption characteristics in the upper gastrointestinal tract. To overcome this, there is increasing interest in developing gastro-retentive formulations and/or formulations that linger in the proximal parts of the small intestine, e.g.

Effects of extracts of commonly consumed food supplements and food fractions on the permeability of drugs across Caco-2 cell monolayers.

Purpose: Extracts made from berries, herbs, and various plant materials, which might possess a range of activities, are used as health promoting products. Because little is known about their effects on the absorption of co-administered drugs, the effects of some food supplements, Finnish berries, and herbs were studied on the permeability of some commonly used drugs.

Methods: The permeabilities of verapamil, metoprolol, ketoprofen, paracetamol, and furosemide were studied across Caco-2 cell monolayers with contemporaneously administered extracts from flax seed, purple loosestrife, and Scots pine bark; bilberries, cowberries, and raspberries; oregano, rosemary, and sage.

Neutron activation-based gamma scintigraphy in pharmacoscintigraphic evaluation of an Egalet constant-release drug delivery system.

This paper is a report from a pharmacoscintigraphic study with an Egalet constant-release system containing caffeine and natural abundance samarium oxide. First the formulation was tested in vitro to clarify integrity during irradiation in the nuclear reactor. Then six healthy male volunteers were enrolled into the in vivo study.

Citric acid as a pH-regulating additive in granules and the tablet matrix in enteric-coated formulations for colon-specific drug delivery.

Colon-specific drug-delivery systems have been extensively investigated over the last decade. The aim of the study reported here was to investigate whether times of commencement of drug liberation and absorption could be controlled by varying the amount of citric acid in granule cores or in the tablet matrix in enteric-coated multiple-unit tablets. One of the most important aims was to determine the optimal amounts and locations of citric acid in formulations intended as drugs targeted at the colon.

Gamma scintigraphic evaluation of the fate of hydroxypropyl methylcellulose capsules in the human gastrointestinal tract.

The fate (movement and disintegration) of hard novel hydroxypropyl methylcellulose (HPMC) two-piece capsules in the human gastrointestinal tract was investigated using a gamma scintigraphic imaging method. Two different prolonged-release formulations without an active ingredient were used. The capsules contained different viscosity grades of HPMC powder (HPMC K100 and HPMC K4M).

Scintigraphic verification of adherence of a chitosan formulation to the human oesophagus.

It is well known that adherence of a drug product, e.g. a gelatine capsule, to the oesophagus can cause oesophageal injury, which can be severe if the medicinal agent has corrosive properties.

Gamma scintigraphic evaluation of the fate of microcrystalline chitosan granules in human stomach.

In several reports of in vitro studies it has been suggested that the mucoadhesive chitosans could be of value in preparing gastro-retentive formulations. The aim of this study was to obtain direct in vivo evidence of whether microcrystalline chitosan (MCCh) formulations acted as gastro-retentive systems in humans. Neutron-activation-based gamma scintigraphy was used to study gastric residence times of MCCh granules in healthy male volunteers.

Evaluation of microcrystalline chitosans for gastro-retentive drug delivery.

In vivo absorption studies were carried out in human volunteers to evaluate whether microcrystalline chitosan (MCCh) granules would be gastro-retentive. Furosemide, which is site-specifically absorbed from the upper gastrointestinal tract, was used as model drug. The rate of release of furosemide in vitro could be prolonged by increasing the molecular weight (M(w)) or amount of MCCh (150 to 240 kDa; 80 to 95%) in the granules, and also by addition of acidic excipients to the formulations.

In vivo evaluation of matrix granules containing microcrystalline chitosan as a gel-forming excipient.

Interest in drug delivery to the gastrointestinal tract by means of chitosan has been increasing. In the study reported, the biopharmaceutical properties of granules containing microcrystalline chitosan (MCCh; molecular weight 150 kDa, degree of deacetylation 75%) were evaluated via bioavailability tests in human volunteers. Ibuprofen and furosemide were used as model drugs.

Development of level A, B and C in vitro-in vivo correlations for modified-release levosimendan capsules.

The aim of this study was to investigate the possibility of developing different levels of correlation between in vitro release and in vivo absorption rate for four modified-release levosimendan capsule formulations. Differences and similarities in the in vitro dissolution curves were compared with pharmacokinetic parameters describing absorption rate. Formulations F, G, H and I differed in the amounts of the delaying excipients alginic acid and HPMC.

In vitro evaluation of microcrystalline chitosan (MCCh) as gel-forming excipient in matrix granules.

Although much research has been carried out into the effects of chitosan and its chemical properties on drug release, less attention has been paid to the effects of its physical properties. The aim of this study was to characterize microcrystalline chitosan (MCCh) as a gel-forming excipient. Matrix granules containing chitosans of differing physicochemical properties (crystallinity, molecular weight, degree of deacetylation) and ibuprofen or paracetamol as model drugs were prepared.

Effect of synthesis parameters of the sol-gel-processed spray-dried silica gel microparticles on the release rate of dexmedetomidine.

The objective of this study was to evaluate the possibilities to control the release rate of dexmedetomidine (DMED) from different spray-dried silica gel microparticle formulations. Microparticles were prepared by spray drying a silica sol polymer solution containing the drug. Drug release was investigated both in vitro and in vivo.

Bioavailability and in vitro oesophageal sticking tendency of hydroxypropyl methylcellulose capsule formulations and corresponding gelatine capsule formulations.

The overall aim of the present study was to widen our knowledge about the biopharmaceutical behaviour of novel hydroxypropyl methylcellulose (HPMC)-based two-piece capsules by comparing them with the classic hard gelatine capsules. Firstly, the tendency of the HPMC capsules to stick to isolated porcine oesophageal preparation was evaluated. The force needed to detach the HPMC capsules from the oesophagus was significantly lower than that for the gelatine capsules (P<0.

Removal of acetaldehyde from saliva by a slow-release buccal tablet of L-cysteine.

High alcohol intake is an independent risk factor for upper gastrointestinal (GI)-tract cancers. There is increasing evidence that acetaldehyde, the first metabolite of ethanol, might be responsible for ethanol-associated carcinogenesis. Especially among Asian heavy drinkers with the ALDH2-deficiency gene, i.

Citric acid as excipient in multiple-unit enteric-coated tablets for targeting drugs on the colon.

Delivery of drugs to the large bowel has been extensively investigated during the last decade. The aim of this study was to investigate whether enteric-coated tablets could be made from enteric-coated matrix granules and drug release targeted to the colon. Whether in vitro drug release rate and in vivo absorption could be delayed by adding citric acid to the granules and/or to the tablet matrix was also studied.

Time-controlled release pseudoephedrine tablets: bioavailability and in vitro/in vivo correlations.

In chronopharmacotherapy, circadian changes in disease symptoms are taken into account. Press-coated, time-controlled release tablets containing pseudoephedrine hydrochloride as a model drug have been formulated and the suitability of this highly soluble drug in relation to the new drug delivery system was evaluated. Hydroxypropylmethylcellulose was used in the coat of the tablet to adjust drug release.

Alkyl-substituted silica gel as a carrier in the controlled release of dexmedetomidine.

The effect of alkyl substitution of the silica xerogel matrix on the release rate of dexmedetomidine was evaluated. Silica sol was processed by either casting or spray drying. When the reaction precursor tetraethylorthosilicate (TEOS) was partially substituted with tri- or dialkoxysilane, the release of dexmedetomidine and degradation of the matrix were decreased compared with 100% TEOS-based gel.