Biomedical subjects

S A Sande

Publications and source records attributed to S A Sande.

10 recordsLinked to original sources

PubMed2002

A formulation development strategy for multivariate kinetic responses.

The purpose of this paper was to evaluate a multivariate strategy for handling time-dependent kinetic data during formulation development. Dissolution profiles were evaluated by the Weibull equation, multiple linear regression (MLR), principal component analysis (PCA), alone and in combination. In addition a soft independent modeling of class analogy (SIMCA) was performed. Employing a typical kinetic model for solid formulations (here Weibull) showed difficulties with the model adaptation, resulting in increased model standard deviation and thereby failure in identifying significant variables. In general, the selection of a kinetic model is crucial for finding the significant formulation variables. Describing the dissolution profile based on MLR models of individual time points described the dissolution rates as a function of formulation variables with good precision. Establishing prediction models made it easy to evaluate effects on the entire dissolution profile. The use of PCA/MLR (PCR) reduced the influence of noise from single measurements in a kinetic profile, since they develop statistical parameters representing the profile without being dependent on a physicochemically-modeled profile. The use of PCA reduced the eight time-point variables to two latent variables (principal components), simplifying the classification of formulations and new samples as well as avoiding unwanted effects of model non-linearities between the factors and responses (model error). The group membership of new samples was demonstrated by SIMCA.

Chemistry, Pharmaceutical↗

PubMed2000

Formulation and characterisation of primaquine loaded liposomes prepared by a pH gradient using experimental design.

The effect of different formulation factors (lipid type, cholesterol, charge, internal buffer capacity, drug-to-lipid incubation ratio) on the encapsulation efficiency and size of primaquine liposomes (SUV's) in response to a pH gradient was investigated by a fractional factorial screen ing design. Three of the factors (charge, internal buffer capacity, drug -to-lipid incubation ratio) were further studied in a Box--Behnken optimisation design. The lipid type was the most important parameter followed by the drug-to-lipid incubation ratio, buffer capacity, cholesterol and charge. Several of the interactions wer e important. In the optimisation design a robust region with high encapsulation efficiency (>95%) was obtained for DSPC: 33.33 mol% cholesterol-liposomes at high internal citrate concentration (200 mM) by maintaining the drug-to-lipid incubation ratio below 0.15:1 (mol:mol) and varying the charge incorporation between 2 and 10%. In order to achieve long-term stability and sterility, the liposomes were lyophilised followed by gamma irradiation. The pH gradient was maintained during this treatment with little chemical degradation of the substances. The final preparation consisted of three separate vials with lyophilised liposomes, solid state primaquine and hydration medium.

Antimalarials↗

PubMed2000

Influence of neutron activation factors on matrix tablets for site specific delivery to the colon.

The impact of the neutron activation procedure, i.e. incorporation of samarium oxide (Sm(2)O(3)) and neutron irradiation, on the compression properties (including the crushing strength) and in vitro dissolution of potential colonic delivery systems based on matrix tablets of amidated pectin (Am.P) or two types of hydroxypropyl methylcellulose (HPMC) was investigated. The neutron activation factors did not influence the compression properties of the tablets. Replacement of magnesium stearate with samarium stearate in directly compressed Am.P tablets to achieve both radiolabelling and lubrication resulted in a greater extent of concentration-dependent reduction of the crushing strength. Dissolution tests demonstrated that irradiation increased the release of the model drug ropivacaine from the tablets. The extent of this increase was unexpectedly low considering the previously observed degradation of the polymer expressed as an irradiation-induced viscosity reduction in solutions prepared from the polymers. Delayed-release coating with Eudragit L 100 protected the HPMC tablets against the release-increasing effect of irradiation until the late phases of release. Sm(2)O(3) retarded the release to a varying extent depending on particle characteristics. Incorporation of Sm(2)O(3) in the coating layer did not influence the release. However, one-third of the radioactivity leached from the coating within 60 min in 0.1 M HCl.

Amides↗

PubMed2000

Development of pectin matrix tablets for colonic delivery of model drug ropivacaine.

The objective of this work was to develop pectin-based matrix tablets for colonic delivery of the model drug ropivacaine, with the future perspective of radiolabelling the system by neutron activation technique for a gamma-scintigraphic study. The aim was to investigate some formulation factors that could reduce the release of the drug in the simulated gastric and intestinal fluids, increase the release in the simulated cecal fluid (with pectinolytic enzymes) and improve the poor compactibility of pectins. For dissolution studies, the flow-through apparatus with sequential dissolution liquids simulating the mouth-to-colon conditions was used. The effect of two pectin types, the incorporation of ethylcellulose as a dry matrix-additive and water or ethanol as granulation liquids were investigated in a study designed as a D-optimal mixture. Amidated pectin (Am.P) produced harder tablets than the calcium salt of pectin (Ca.P) and was more susceptible to enzymatic degradation. Addition of ethylcellulose increased the tablet strength and the dissolution rate. Furthermore, directly compressed Am.P tablets were produced by addition of coarse or micronised qualities of ethylcellulose. The latter improved the crushing strength markedly imposing a marginal release-reducing effect. Coating this formulation with Eudragit((R)) L 100 reduced the release in the simulated upper GI conditions without interference with the subsequent enzymatic activity.

Amides↗

PubMed1999

Influence of neutron irradiation on Eudragit coated tablets: validation of neutron activation II.

The in vitro characteristics of enteric coated acetylsalicylic acid tablets and cores were compared before and after irradiation with thermal neutrons, 2, 4, 7 or 15 min at 1.1.1013 neutrons cm-2s-I. The irradiation procedure affected the coated formulation to a greater extent than the cores. Drug release from tablets was already affected after 2 min of exposure, whereas the cores showed no significant inhibition of release until after 15 min of irradiation, leading to the conclusion that the effects of irradiation were caused by a combination of changes both in the core and the coating. Both tablets and cores showed an increase in the disintegration time following irradiation. Scanning electron micrographs (SEM) of non-irradiated cores/tablets and cores/tablets irradiated for 15 min, showed clear differences in the structure of the surface. SEM of the tablets irradiated for 15 min, showed that the irradiation had caused the film to loosen from the core in several places. SEM of the cross-sections of both irradiated tablets and cores showed a partially melted surface above stacked layers with reduced porosity.

Acrylic Resins↗

PubMed1999

Influence of the coating thickness and type of oral delivery system (tablets, pellets) on the stability towards degradation by neutron irradiation. Validation of neutron activation III.

Enteric coated dexchlorpheniramine maleate (DCPA) tablets and pellets with varying coating thickness were subjected to several in vitro tests after irradiation by thermal neutrons in a flux of 1. 1 x 10(13) n cm-2 s-1 for 2, 4 or 15 min. The appearance of the tablet formulation changed extensively after exposure of the tablets to pile radiation. The irradiation caused the film to loosen from the surface of the core, indicating the generation of gases during the irradiation process. Already after irradiating the tablets for 2 min the disintegration and dissolution behaviour were significantly changed. The extent of tablet damage increased with increasing time of exposure and increasing thickness of the coating. Compared with the tablet formulation, the cores could resist a larger amount of irradiation since dissolution behaviour of the cores was only affected after 15 min of irradiation. This indicates that the irradiation procedure initially affects the coating of the formulation. Although the dissolution behaviour of the pellet formulations changed significantly after the irradiation procedure, the changes were too small to be attributed exclusively to radiation damage.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1999

Influence of neutron activation factors on the physico-chemical properties of suppositories and their excipients.

The effect of the neutron activation factors, i.e., admixture of samarium oxide (Sm2O3) and irradiation time, on the physico-chemical properties of the raw materials and the in vitro dissolution and disintegration of hydrophilic and lipophilic suppositories was investigated. It was possible to expose the pure bases and the model drugs (5-aminosalicylic acid [5-ASA] and ropivacaine hydrochloride) to 1 min of neutron irradiation in a flux of 1.1.1013 n cm-2s-1. The dissolution and disintegration of the corresponding suppositories showed that the physico-chemical properties and the fraction of incorporated drug together with the lipophilic/hydrophilic nature of the base were important factors. Sm2O3 increased the disintegration time of hydrophilic suppositories containing 5-ASA, while the dissolution of both drugs from these formulations remained unchanged. Sm2O3 did not alter the disintegration time of the lipophilic formulations, but it reduced the dissolution of both drugs from these suppositories. Irradiation induced different behaviour in the different bases.

Amides↗

PubMed1999

Effects of thermal neutron irradiation on some potential excipients for colonic delivery systems.

Different excipients, which are currently being studied for colon delivery systems, were examined with respect to their stability toward neutron irradiation as a potential method of radiolabeling the formulations for gamma-scintigraphic studies. Three different pectin and four different hydroxypropyl methylcellulose (HPMC) types, in addition to two types of polymethacrylate films, were exposed to 1, 2, and 3 min of thermal neutron irradiation in a flux of 1.1 x 10(13) n cm-2 s-1. The physicochemical characteristics of pectins and HPMCs and the mechanical properties of the polymethacrylate films were examined after the radioactivity of the samples had declined to background levels. Methods included ultraviolet (UV) and Fourier transform infrared (FTIR) spectroscopy, pH measurements, loss on drying, thermogravimetric analysis (TGA), viscosimetry, gas chromatographic (GC) analysis of pectin monosaccharides, and tensile strength testing of the films. The results suggest that pectins and HPMCs undergo degradation, as expressed by a significant reduction in the dynamic and intrinsic viscosities of the samples. Generally, HPMCs were more sensitive than pectins to neutron irradiation. However, calcium pectinate proved to be the most sensitive among all the investigated polymers. Both polymethacrylate films (Eudragit L and S) resisted loss of mechanical properties following 1 and 2 min of neutron irradiation, whereas irradiation for 3 min implied significant changes in the appearance and the mechanical properties of Eudragit L films. As a conclusion, neutron irradiation results in dose-dependent degradation of the investigated polysaccharides and polymethacrylates. The consequences on the in vitro behavior of a formulation containing such polymers are discussed.

Chromatography, Gas↗

PubMed1994

Photoreactivity of biologically active compounds. VII. Interaction of antimalarial drugs with melanin in vitro as part of phototoxicity screening.

The drugs commonly used in the treatment of malaria are photochemically unstable. Several of these compounds accumulate in melanin-rich tissues and cause toxic reactions which may be light induced. As part of the screening of the photochemical properties and phototoxic capabilities of antimalarials, the in vitro interaction of eight antimalarials with melanin was studied. The dissociation constant for the drug-melanin complex and the relative number of binding sites on melanin were estimated for six of the drugs using a curve-fitting program. The reaction rate for the formation of the melanin-drug complex was determined, and the complexes were further characterized by zeta potential measurements.

Antimalarials↗

PubMed1991

Characterization of enteric-coated tablets and pellets by two in vitro dissolution methods and by scanning electron microscopy.

The in vitro dissolution rates of enteric-coated pellets and tablets containing dexchlorpheniramine maleate (DCPM) were obtained using the USP XXI paddle and a flow-through method. Pellets were produced by extrusion and spheronization. Tablets were produced by direct compaction, and by wet granulation. The products were coated with different amounts of Eudragit L30D using fluid-bed technology. Onset of release, determined by fitting of the Weibull function, was the only factor found to be affected by the amount of coating of the tablets. For pellets, both onset of release and dissolution rate showed significant differences. Scanning electron microscopy was used to study the effect of different dissolution media on the coating. Acidic medium was found to alter the coating surface, but the coating did not rupture during the time used in this study.

Dosage Forms↗