Water-soluble Carrier Research Articles

Preparation of sustained-release suppositories of indomethacin using a solid dispersion system and evaluation of bioavailability in rabbits.

Sustained-release suppositories of indomethacin (IM) were prepared by the use of a solid dispersion system. As the suppository base, we used a solid matrix of polyethylene glycol 2000(PEG) as a water-soluble carrier and hydroxypropylmethylcellulose phthalate (HP55) as a poorly water-soluble carrier. It was observed by X-ray diffractometry that IM was uniformly dispersed in amorphous state in the matrix suppositories. The rectal administration of 20% HP55 matrix suppositories (M-20-5) in rabbits resulted in both fast-release and sustained-release characteristics as well as good bioavailability. The sustained release of IM from the matrix suppositories was attributed to the formation of a network structure of HP55 which dissolved more slowly than PEG.

Studies on sustained-release dosage forms. III. Preparation of nifedipine suppositories and bioavailability in rabbits.

By the use of solid dispersion systems, suppositories having both a fast release and a sustained release of nifedipine were developed. Namely, cellulose acetate phthalate (CAP)-polyethylene glycol (PEG) matrix was prepared as a suppository base by using PEG 4000 as a water-soluble carrier and CAP as a poorly soluble carrier. Conventional suppositories (use of PEG 4000 alone as a base : C-0), three kinds of CAP-PEG matrix suppositories (use of 5, 10 and 15% (w/w) CAP in the matrix : M-5, M-10 and M-15) and double layer suppositories including nifedipine only in the outside layer (use of 15% CAP in the matrix as a base : D-15) were prepared, and the sustained-release effect and bioavailability of each suppository were examined in rabbits. The M-5 as well as C-0 produced a sharp peak of plasma concentration of nifedipine and did not give a sustained-release effect. The M-10 gave a sustained-release effect, but it was not a desirable preparation because it developed many cracks and broke easily. The M-15 gave a low and plateau plasma level of nifedipine and had no cracks, but the extent of bioavailability was very small. The D-15 enhanced the bioavailability of nifedipine and also gave a sustained-release plasma level of nifedipine. Therefore, it appeared that D-15 was a suitable preparation for our purpose.

Water-soluble carrier proteins having carboxyl spacer groups.

Three water-soluble bovine serum albumin derivatives with carboxyl spacer groups have been synthesized as carrier proteins for direct preparation of conjugates between proteins and low molecular haptens with amino groups. N-Glycylaminomethanesulfonic acid, a newly developed solubilizing reagent for proteins, was first introduced into bovine serum albumin through its carboxyl groups. After the methylation of carboxyl groups remaining unreacted in the modified albumin, N-succinylglycine and N-bromoacetyl-β-alanine, both carboxyl spacer reagents, were reacted with the amino or imidazole groups of the modified albumin, respectively, to give two water-soluble albumin derivatives. Another water-soluble albumin derivatives. Another water-soluble albumin derivative was obtained by treating the modified albumin with N-bromoacetyl-β-alanine followed by amidination of the remaining amino groups of the albumin with methylacetimidate. Glycine ethyl ester, selected as a model hapten that has an amino group, was reacted with these albumin derivatives to form conjugates, and 4-15 ester moieties can be incorporated into one molecule of the albumin derivatives without loss of their water-solubility.

ENHANCED DISSOLUTION RATE OF IBUPROFEN USING SURFACTANTS AND WATER SOLUBLE CARRIERS

The influence of some non-ionic surfactants as well as polyethylene glycol 6000 and dextrose as water soluble carrier, on the dissolution of poorly soluble drug, ibuprofen, was studied. Surfactants produced better drug release than the polyethylene glycol and dextrose with the drug carrier ratio studied. TLC and IR studied ruled out any interaction between the drug and any of the additives used. In addition, the bulkness of the drug was not affected by the amount of surfactants added, as being found with dextrose and polyethylene glycol 6000.

Stabilization of proteins by modification with water-soluble polysaccharides

The effect of chemical modification by water-soluble polysaccharides on the thermostability of basic pancreatic trypsin (EC 3.4.21.4) inhibitor (BPTI) has been studied. Stabilization of BPTI was achieved by multipoint protein-matrix interaction with the formation of new linkages. The nature of the formed bonds is covalent after modification by bi- and/or polyfunctional reagents and ionic after preparation of polyelectrolytic complexes between BPTI and soluble polysaccharides. The thermostability of BPTI increased because of protein-protein interaction on the water-soluble carrier. This approach may be generally employed for the preparation of stabilized water-soluble proteins.

Combined Water-Soluble Carriers for Coprecipitates of Tolbutamide

A study was conducted on the influence of single and combined carriers on the dissolution rate of tolbutamide from its coprecipitates. All of the water-soluble carriers investigated enhanced the dissolution rate of tolbutamide, but the combination of 40% polyethylene glycol 6000-60% dextrose as the carrier for a 1:1 coprecipitate yielded the most rapid dissolution of tolbutamide. Other carriers used were polyethylene glycol 6000, polyethylene glycol 4000, dextrose, and mannitol, alone or combined in various proportions.

The Influence of Various Dispersing Agents on the Dissolution Rate of Hydrochlorothiazide

AbstractThe solvent and melt methods were employed to prepare solid dispersions with various water soluble carriers and sparingly soluble drug, hydrochlorothiazide. The carriers investigated included dextrose, sorbitol, tartaric acid and urea. Dispersion with urea was superior to other carriers in releasing the drug into solution. Dextrose - melt showed decomposition of the drug. Sorbitol drug physical mixture produced a faster rate of dissolution of the drug than the melt dispersions. The eutectic mixture of urea and drug cooled at room temperature (28°) produced a faster dissolution rate of the drug than the mixture cooled at -2°.

Evaluation of various zinc sources for rice grown on alkali soil

AbstractA field experiment was conducted on a Zn deficient alkali soil to compare the efficiency of soluble and sparingly water soluble Zn carriers at 0,11 and 22 kg Zn/ha. The growth of the rice crop was poor in no Zn plots. Zinc application markedly increased the yield and Zn uptake by rice. This resulted from a significant increase in Zn concentration in plants from deficient to sufficient levels. The rice grain yields in zinc sulphate treatments were significantly better than zinc oxide and zinc frits. The relative efficiency of Zn varied in the order; zinc sulphate>mixture of multi‐micronutrient cations>zinc oxide = Zn‐frits. The efficiency of zinc oxide and Zn‐frits at 22 kg Zn/ha was equal to that of 11 kg Zn/ha from zinc sulphate.

Bioavailability Monograph-Digitoxin

Amorphous solid dispersions are one of the most promising strategies to improve the oral bioavailability of sparingly water-soluble drugs. Drug particle size reduction improved the drug wettability and bioavailability significantly. Poorly soluble drugs may benefit from formulation approaches that overcome poor solubility and dissolution rate limited bioavailability. The solubility of a compound in the amorphous form is higher than the more stable crystalline form because the Gibbs free energy is higher. In addition, glasses or amorphous forms are kinetically trapped high energy disordered materials that lack the periodicity of crystals but behave mechanically as solids. Lipophilic molecules, especially those belonging to the biopharmaceutics classification system (BCS) class II and IV, dissolve slowly, like incomplete release from the dosage form, poor bioavailability, increased food effect, and high inter-patient variability. Hence, several formulation approaches can be taken to improve the solubility and dissolution of poorly water-soluble compounds, such as formulating the API in an amorphous form. Amorphous solid dispersions of poorly water-soluble drugs with water-soluble carriers have been reduced the incidence of these problems and enhanced dissolution. This review is mainly focus on advantages, methods of preparation, and characterization of the amorphous solid dispersion.

Intermembrane electron transport in the absence of added water-soluble carriers

Electron transport from untreated to mersalyzed microsomal vesicles at the level of NADH-cytochrome b 5 reductase or cytochrome b 5 has been demonstrated in the absence of added water-soluble electron carriers. A similar effect was shown in the systems “intact mitochondria — mersalyzed microsomes” and “mersalyzed mitochondria— untreated microsomes”. No measurable electron transport between intact and mersalyzed particles of inner mitochondrial membrane was found. The obtained data suggest that the capability to carry out intermembrane electron transfer is specific for NADH-cytochrome b 5 reductase and/or cytochrome b 5, localized in microsomal and outer mitochondrial membranes.

The Influence of Various Dispersion Methods on the Rate of Dissolution of Sulfabenzamide

The solvent and melt methods were employed to prepare solid dispersions with various water soluble carriers and a slightly soluble drug, sulfabenzamide. The carriers investigated included citric acid, succinic acid, dextrose, polyethylene glycol 6000, mannitol and urea. Dispersions with dextrose were superior to other carriers in releasing the drug into solution. Melts with both dextrose and urea produced faster rates of dissolution of sulfabenzamide than the coprecipitates from the solvent method. With mannitol and polyethylene glycol 6000, the coprecipitates produced a faster rate of dissolution of the drug than the melt dispersions.

Dissolution Enhancement of Domperidone Using Water Soluble Carrier by Solid Dispersion Technology

Domperidone is a highly water insoluble drug exhibiting poor dissolution pattern. This is the cause for its poor absorption. Currently, several products of this drug substance is available in the market. Solid dispersions of domperidone were prepared using different ratios of polyvinylpyrrolidone as carrier by kneading method. They were evaluated for drug content, intactness of the drug in the formulation and dissolution. IR spectral and DSC studies were used to characterize the solid dispersion and to study the possibility of complexation of drug with carrier. The dissolution of domperidone from the solid dispersions exhibited higher rates of dissolution and dissolution efficiency values over that of pure drug