Biomedical subjects

K Amighi

Publications and source records attributed to K Amighi.

16 recordsLinked to original sources

PubMed2006

Development and evaluation of new multiple-unit levodopa sustained-release floating dosage forms.

This work relates to the development and the in vitro evaluation of sustained-release minitablets (MT), prepared by melt granulation and subsequent compression, which are designed to float over an extended period of time. Levodopa was used as a model drug. The importance of the composition and manufacturing parameters of the MT on their floating and dissolution properties was then examined. The investigation showed that MT composition and MT diameter had the greatest influence on drug release, which was sustained for more than 8h. By using the same formulation, the best floating properties were obtained with 3mm MT prepared at low compression forces ranging between 50 and 100N. Their resultant-weight (RW) values were always higher than those obtained with a marketed HBS dosage form within 13h. When they were filled into gelatin capsules, no sticking was observed. By evaluating the dissolution profiles of levodopa at different pH values, it was found that dissolution profiles depend more on the prolonged-release ability of Methocel K15M than on the pH-dependent solubility of levodopa. Finally, the robustness of the floating MT was assessed by testing the drug release variability in function of the stirring conditions during dissolution tests.

Adhesiveness↗

PubMed2006

Preparation and in vitro/in vivo evaluation of nano-sized crystals for dissolution rate enhancement of ucb-35440-3, a highly dosed poorly water-soluble weak base.

Ucb-35440-3 is a new drug entity under investigation at UCB S.A. Due to its physicochemical characteristics, the drug, a poorly water-soluble weak base, shows poor solubility and dissolution characteristics. In rat, the low oral bioavailability (F < 10%) is largely due to poor absorption. In order to enhance the solubility and dissolution characteristics, formulation of ucb-35440-3 as nanocrystals has been achieved in this study. Nanoparticles were prepared using high pressure homogenization and were characterized in terms of size and morphology. In vitro dissolution characteristics were investigated and compared to the un-milled drug in order to verify the theoretical hypothesis on the benefit of increased surface area. In vivo pharmacokinetic evaluation of ucb-35440-3 nanoparticles was also carried out on rats. Crystalline state evaluation before and following particle size reduction was conducted through polarized light microscopy and PXRD to denote any possible transformation to an amorphous state during the homogenization process. Drug chemical stability was also assessed following homogenization. The dissolution rate increased significantly at pH 3.0, 5.0 and 6.5 for ucb-35440-3 nanoparticles. However, the pharmacokinetic profile obtained yielded lower systemic exposure than the un-milled compound (in fed state), this although being thought to be the consequence of the drug and formulation characteristics.

Administration, Oral↗

PubMed2006

In vitro and in vivo evaluation of floating riboflavin pellets developed using the melt pelletization process.

Floating pellets were prepared using the melt pelletization process in a Mi-Pro high shear mixer (Pro-C-epT, Belgium). Formulations were based on a mixture of Compritol and Precirol as meltable binders and on the use of sodium bicarbonate and tartaric acid as gas-generating agents. Good floating abilities were obtained by using the gas-generating agents in both the inner matrix and the outer coating layer of the pellets. In vitro evaluation of floating capability was performed both by using the resultant weight apparatus and by counting floating pellets at the surface of beakers containing 0.1N HCl solution, in vivo evaluation of floating pellets capabilities was also performed. Riboflavin-containing floating pellets (FRF) were administered orally to nine healthy volunteers versus non-floating pellets (NFRF). Volunteers were divided in two groups, fasted group (n=4) 729 kcal and fed group (n=5) 1634 kcal as the total calorie intake on the testing day. An increase of urinary excretion of riboflavin was observed when the volunteers were dosed with the floating pellets, especially after feeding. As riboflavin has a narrow window of absorption in the upper part of small intestine, this phenomenon could be attributable to the gastric retention of floating pellets.

Adult↗

PubMed2005

Amodiaquine polymeric membrane electrode.

The construction and electrochemical response characteristics of two types of poly(vinyl chloride) (PVC) membrane sensors for the determination of amodiaquine hydrochloride (ADQ.2HCl) are described. The sensing membrane comprised an ion-pair formed between the cationic drug and sodium tetraphenyl borate (NaTPB) or potassium tetrakis(4-chlorophenyl) borate (KTCPB) in a plasticized PVC matrix. Eight PVC membrane ion-selective electrodes were fabricated and studied. Several plasticizers were studied namely, dioctyl phthalate (DOP), 2-nitrophenyl octyl ether (NPOE), dioctyl phenylphosphonate (DOPP) and bis(2-ethylhexyl)adipate (EHA). The sensors display a fast, stable and near-Nernstian response over a relative wide ADQ concentration range (3.2 x 10(-6) to 2.0 x 10(-2) M), with slopes comprised between 28.5 and 31.4 mV dec(-1) in a pH range comprised between pH 3.7 and 5.5. The assay of amodiaquine hydrochloride in pharmaceutical dosage forms using one of the proposed sensors gave average recoveries of 104.3 and 99.9 with R.S.D. of 0.3 and 0.6% for tablets (Malaritab) and a reconstituted powder containing ADQ.2HCl, respectively. The sensor was also used for dissolution profile studies of two drug formulations. The sensor proved to have a good selectivity for ADQ.2HCl over some inorganic and organic compounds, however, berberine chloride interfered significantly. The results were validated by comparison with a spectrophotometric assay according to the USP pharmacopoeia.

Adipates↗

PubMed2005

Preparation and characterization of nanocrystals for solubility and dissolution rate enhancement of nifedipine.

Poorly water-soluble drugs such as nifedipine (NIF) (approximately 20 microg/ml) offer challenging problems in drug formulation as poor solubility is generally associated to poor dissolution characteristics and thus to poor oral bioavailability. In order to enhance these characteristics, preparation of nifedipine nanoparticles has been achieved using high pressure homogenization. The homogenization procedure has first been optimized in regard to particle size and size distribution. Nanoparticles were characterized in terms of size, morphology and redispersion characteristics following water-removal. Saturation solubility and dissolution characteristics were investigated and compared to the un-milled commercial NIF to verify the theoretical hypothesis on the benefit of increased surface area. Crystalline state evaluation before and following particle size reduction was also conducted through differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) to denote eventual transformation to amorphous state during the homogenization process. Through this study, it has been shown that initial crystalline state is maintained following particle size reduction and that the dissolution characteristics of nifedipine nanoparticles were significantly increased in regards to the commercial product. The method being simple and easily scaled up, this approach should have a general applicability to many poorly water-soluble drug entities.

Calcium Channel Blockers↗

PubMed2005

[Bioequivalence in vitro evaluation of some antibacterial generic dosage forms].

In this work, bioequivalence between generic and corresponding original brand-name dosage forms of some antibacterial drugs, frequently prescribed in developing countries, have been examined using in vitro dissolution testing. For this purpose, tablet or hard capsule formulations of five active substances (amoxycillin, ampicillin, co-trimoxazole (sulphamethoxazole/trimethoprim), metronidazole and penicillin V) have been retained. For each active substance, batch samples of three generic and one test formulations have been submitted to the pharmaceutical quality control and dissolution testing. Results obtained have shown that all samples examined met the specifications of quality edited by the pharmacopeias. On the other hand, interchangeability between generic and corresponding test formulations should be possible since their dissolution profiles are superposables enough.

Anti-Bacterial Agents↗

PubMed2004

Poly(N-isopropylacrylamide) copolymers for constant temperature controlled drug delivery.

In the course of the development of a new drug delivery concept, four thermosensitive copolymers of poly(N-isopropylacrylamide) (PNIPAAm), with phase transition temperature slightly higher than 37 degrees C, were synthesised and used as time-controlled drug delivery agents. For this purpose, compression-coated tablets coated with the thermosensitive copolymers and containing Na2SO4 were prepared and in vitro dissolution tests were performed at constant physiological temperature, the lag time before drug release being controlled by the amount of Na2SO4 incorporated into the form. Due to the salting out effect, the lag time was increased by up to 80-90% for PNIPAAm-co-NVA and PNIPAAm-co-MVA coated tablets.

Acrylic Resins↗

PubMed2003

Surfactant induced drug delivery based on the use of thermosensitive polymers.

A novel approach of controlled drug delivery using thermosensitive polymers is developed in this paper. The drug release occurs at physiological temperature, at which the polymer is normally not soluble, and no medium temperature changes are required to bring about the delivery. For this purpose benefit is taken from the specific binding properties of some anionic surfactants and poly(N-isopropylacrylamide) (PNIPAAm) in order to modify the dissolution properties of PNIPAAm and of a copolymer with N-vinyl-acetamide (NVA), and so to induce the release of a drug contained in compression coated tablets. The influence of surfactant type and amount on the drug release rates and lag times from tablets coated with PNIPAAm or with the copolymer are discussed. It was found that the lag time is influenced by the surfactant species and amount. When use is made of a copolymer as coating agent, it is possible to bring about the release of the drug by incorporating only a very small amount (as low as 2%) of sodium dodecyl sulfate (SDS) in the coating.

Acrylic Resins↗

PubMed2001

Effect of some physiological and non-physiological compounds on the phase transition temperature of thermoresponsive polymers intended for oral controlled-drug delivery.

Poly-N-isopropylacrylamide (PNIPAAm) thermosensibility makes this polymer a very attractive candidate for controlled drug delivery systems. The polymer possesses a lower critical solution temperature (LCST) which was found to be around 32 degrees C in pure water, but which can be affected by the medium composition, i.e. presence of salts or surfactants. The knowledge of the effects of such substances on the LCST is very important while using PNIPAAm as a controlled drug delivery agent. The influence of a number of physiological and non-physiological salts and surfactants has been studied. The results obtained show that the addition of salts provokes an important decrease of the LCST of the polymer (salting out effect). A strong influence of the valence and of the size of the anions of the halide group was found. As to the surfactants, according to their type and concentration, a decrease or an increase of the LCST or even no effect at all were found. The effect of the GI secretions on the PNIPAAm phase separation temperature is also discussed.

Acrylic Resins↗

PubMed2001

[New research on the significance of polymers in pharmaceutical formulations].

During these last few decades, a lot of work has been made in pharmaceutical area in order to control the drug delivery from various pharmaceutical dosage forms. The use of polymers in pharmaceutical technology have led to the development of the first drug delivery systems proposed in order to prolong or to delay the drug delivery, or to enhance drug release for drugs showing bioavailability shortcomings. The wide range of polymers available for pharmaceutical use, their low reactivity towards drugs and other formulation ingredients and their safe nature, have permitted a widespread use of polymers to improve manufacturing processes or for the formulation of pharmaceutical dosage forms for various administration routes. More over, the preparation of new polymeric materials by the synthesis of new polymers with unique properties or by the modification of available natural or synthetic polymers, offer to the formulator a wide range of applications in order to optimise the drug delivery for each specific case.

Chemistry, Pharmaceutical↗

PubMed2000

Effect of pectinolytic enzymes on the theophylline release from pellets coated with water insoluble polymers containing pectin HM or calcium pectinate.

Theophylline pellets were coated with cellulosic (Aquacoat ECD 30, Surelease clear) or acrylic (Eudragit NE30D, RS30D) polymer aqueous dispersions, containing 10% (related to the insoluble polymer content) of pectin HM or calcium pectinate, using a Uni-Glatt fluidized-bed coating apparatus. When commercial pectinolytic enzymes were added to the dissolution media (0.05 M acetate - phosphate buffer, pH 6.0), the release of theophylline from the coated pellets was generally slower than that observed in the media without enzymes. The enzymatic slowing down of the drug release, depending on the type of the aqueous polymer dispersion used, is more important with mixed Eudragit NE/calcium pectinate coated pellets. The results obtained have been examined with regard to the validity of the approach based on the combination of pectins and the insoluble polymer aqueous dispersions intended for specific-delivery of drugs to the colon. The mechanism of the hydrophilic drug release from pellets coated with insoluble polymer aqueous dispersions containing an aqueous gel-forming polymer has been also discussed.

Absorption↗

PubMed2000

Studies of pectin HM/Eudragit RL/Eudragit NE film-coating formulations intended for colonic drug delivery.

Theophylline pellets were coated with Eudragit NE30D aqueous dispersions, containing various pectin HM/Eudragit RL30D ionic complexes, using an Uni-Glatt fluidized-bed apparatus. Dissolution studies were then carried out on the coated pellets at pH 6.0, in absence and in presence of commercial pectinolytic enzymes. The theophylline release from the coated pellets, after an initial latency phase, occurred linearly as a function of time. The theophylline release rate was dependent on the pectin HM content of the complexes incorporated in the coatings. The lowest theophylline release from the coated pellets was obtained when the pectin HM content of the complexes was 20.0% w/w (related to Eudragit RL), i.e. when the complexation between pectin HM and Eudragit RL is optimal. The theophylline release from the coated pellets was slower in presence of the pectinolytic enzymes when the pectin content of complexes is higher than 20% w/w. On the other hand, the effect of the enzymes induced an increase of the theophylline release when the pectin HM content of the coatings ranged between 10.0 and 15.0% w/w (related to Eudragit RL).

Acrylic Resins↗

PubMed1999

Influence of melting and rheological properties of fatty binders on the melt granulation process in a high-shear mixer.

The preparation of granules by melt granulation was investigated using a laboratory-scale high-shear mixer (Pellmix PL 1/8) and binary mixtures containing lactose and different lipidic binders, namely, Compritol 888, Cutina HR, or Precirol ATO5. During the process, the product temperature and the impeller motor power consumption were monitored. On the other hand, the melting behavior (thermal analysis) and the rheological properties (controlled stress capillary rheometer) of the different lipophilic binders were also determined. The granule formation was shown to be quite effective at product temperatures even below the melting point of the lipidic binder, that is, when the binder is sufficiently softened to be deformed by the very high shearing forces developed in the high-shear mixer. On the other hand, the performance of lipidic binders during the melt granulation process was shown to be closely dependent on their melting and rheological properties. The granule growth rate was shown to be higher when the binder melting range is narrow and the influence of temperature on the viscosity of the unmelted product is high.

Calorimetry, Differential Scanning↗

PubMed1998

Peroral sustained-release film-coated pellets as a means to overcome physicochemical and biological drug-related problems. I. In vitro development and evaluation.

In vitro preformulation testing has shown that the solubility and dissolution rate of the model drug compound ucb 11056 are highly pH dependent. Considering this, different sustained-release (SR) oral dosage forms of ucb 11056 were developed aiming to obtain the most constant and complete release of the drug during transit in the gastrointestinal (GI) tract. Classical approaches based on the use of SR formulations such as hydrophilic matrix tablets or pellets coated with one film-forming polymer (Eudragit NE30D or L30D-55) did not fulfill all expectations on the basis of their in vitro evaluation, i.e., the drug release and pattern remained highly dependent on the pH of the dissolution medium. Therefore, taking advantage of the flexibility of release adjustment obtainable from coating of pellets with different kinds of pH-sensitive film layers, a quite satisfactory pH independence of the release characteristics was obtained using formulation blends of neutral and anionic acrylic polymers. For the selected SR pellets batch 15 coated with NE30D/L30D-55 (7:3), the tridimensional topographic representation of the drug release versus time and pH showed that, notwithstanding the pH-dependent aqueous solubility of the drug, the release profiles were relatively homogeneous for any pH value ranging between 1 and 7.

Acrylic Resins↗

PubMed1998

Peroral sustained-release film-coated pellets as a means to overcome physicochemical and biological drug-related problems. II. Bioavailability and tolerance assessment in dogs.

Sustained-release (SR) dosage forms consisting of pellets coated with different pH-sensitive film layers, previously optimized in vitro with regard to pH independence of their drug release characteristics, were evaluated in vivo after single administration to Beagle dogs. In vivo performances were compared to those of a nonoptimized SR matrix tablet and a reference instant release (IR) capsule, in terms of the observed plasma pharmacokinetic profiles for the parent drug (ucb 11056) and its primary metabolite (ucb 26201), the bioavailability results, and the drug tolerance data. All SR dosage forms were seen to be effective in prolonging the relatively short biological half-life of the compound and in reducing the incidence of concentration-related side-effects, e.g., emesis, and of behavioral symptoms, e.g., restlessness, discomfort, and indisposition. The film-coated SR pellets offer a number of advantages over the monolithic SR matrix system in terms of a drug delivery pattern less dependent on pH changes in the gastrointestinal (GI) tract, a higher flexibility for adjusting and controlling the pharmacokinetic profiles, and a consequently more efficient approach for keeping all concentration-related side-effects under control.

Administration, Oral↗

PubMed1995

Preparation of controlled-release coevaporates of dipyridamole by loading neutral pellets in a fluidized-bed coating system.

PURPOSE: The purpose of this study was to demonstrate that it is possible to prepare controlled-release drug-polymer coevaporates on an industrial scale, omitting the recovery problems and the milling and sieving processes encountered when coevaporates are prepared by the conventional solvent-evaporation technique. METHODS: Controlled-release coevaporates were prepared by spraying organic solutions of dipyridamole-Eudragit blends onto neutral pellets using the fluidized-bed coating method. Enteric acrylic polymers Eudragit L100-55, L, and S were used as dispersing agents and drug/polymer ratio 2:8 was selected for all formulations. Polarized light microscopy, X-ray diffraction spectroscopy, and differential scanning calorimetry were used to determine whether the drug was amorphous or crystalline in the coating films. Moreover, in vitro dissolution tests were performed on the dipyridamole coated pellets in test media simulating the pH variations in the GI tract and the results were compared to the release data obtained from coevaporates prepared by the conventional solvent-evaporation method. RESULTS: All the results clearly indicate that dipyridamole is amorphous in the coating films deposited on neutral pellets as well as in coevaporate particles obtained by the conventional solvent-evaporation method. When the release patterns of the dipyridamole coated pellets are compared to those of the drug coevaporate particles prepared with the same enteric acrylic polymers, the results show similar dissolution trends. CONCLUSIONS: The results obtained indicate that pelletization can be considered as a method of choice for pilot plant and/or full-scale production of controlled-release dosage forms based on the formation of amorphous solid dispersions.

Calorimetry, Differential Scanning↗