Biomedical subjects

Lawrence H Block

Publications and source records attributed to Lawrence H Block.

5 recordsLinked to original sources

PubMed2003

Spray-dried chitinosans. Part I: preparation and characterization.

PURPOSE: Physicochemical and micromeritic characterization of chitinosans. METHODS: Chitinosans subjected to N-deacetylation and depolymerization were characterized for degree of N-deacetylation (DD), molecular weight (MW), pK(a), particle size determination and morphology, tap/bulk density measurements, surface area determinations, and determination of flow properties. RESULTS: The chitinosan DDs and MWs were dependent on the processing conditions and ranged from 66 to 89% and 2-522 kDa, respectively. Chitinosan particle sizes and shapes were dependent on drying conditions (range 8-465 microm). Spray-dried chitinosans were spherical and had smaller particle sizes than the non-spray-dried materials which were irregularly shaped particles. Higher density values were obtained for processed materials than those for the raw material. Lower specific surface areas were observed for non-spray-dried chitinosans (0.28-1.59 m(2)/g) than for spray-dried chitinosans (0.74-3.01 m(2)/g). Weight variation of chitinosan tablets indicated that spray-dried chitinosans possessed improved flow characteristics as compared with tray-dried chitinosans. CONCLUSIONS: The effect of drying method employed in chitinosan manufacture, i.e. spray versus tray drying, on the physicochemical and micromeritic properties of the resultant chitinosans were evaluated. Although the drying methods did not significantly influence the physicochemical properties, they affected the micromeritic properties of the resultant chitinosans.

Biopolymers↗

PubMed2003

Spray-dried chitinosans. Part II: in vitro drug release from tablets made from spray-dried chitinosans.

PURPOSE: Application of spray-dried chitinosans as excipients for use in drug delivery systems was explored. METHODS: Spray- and tray-dried chitinosans previously N-deacetylated and depolymerized were used. Directly compressed tablets (200mg) containing tetracycline, chitinosan, and magnesium stearate were prepared. The tablets were characterized for dimensions, weight, friability, crushing strengths, disintegration, and dissolution. RESULTS: The tablet weights, thickness, and diameters were not affected by the chitinosan selected (P>0.05). Friability of tablets containing tray-dried chitinosans was generally higher (and crushing strengths were lower) than tablets containing spray-dried chitinosans. Chitinosan molecular weight, degree of N-deacetylation, and drying method used, significantly affected crushing strengths (P<0.0001). Disintegration times were affected only by the type of chitinosan (P<0.0001) but not by the drying method used (P>0.9). Dissolution from tablets was significantly affected by the chitinosan type (P<0.025), but not affected by the drying method (P>0.5). CONCLUSIONS: Spray drying improved binding functionality of chitinosans, thereby enhancing the tablet crushing strength; however, friability, disintegration, and dissolution profiles were not significantly affected. The data obtained from this study support the usefulness of spray-dried chitinosans as excipients for use in drug delivery systems.

Chitin↗

PubMed2003

Chitinosan-drug complexes: effect of electrolyte on naproxen release in vitro.

The purpose of this study was to examine the potential use of electrolytes to control naproxen sodium (I) release from chitinosan (II) tablets. An ANOVA was employed to evaluate the effects of molecular weight (MW) of II, electrolyte valence (EV), and pH of the dissolution medium on I's release. The intrinsic dissolution rates and saturation solubilities of I were determined at each of the pHs used. Directly compressed tablets were prepared from admixtures containing: I, NaCl, CaCl(2), or AlCl(3), Mg stearate, and II. The tablets were characterized for their dimensions, crushing strengths, friability, disintegration times, and in vitro dissolution profiles. The slopes of the log-log cumulative percent released-time curves (t=0-5 h) were compared using ANOVA. Based on the ANOVA, each of the variables-chitinosans, EVs, and pHs-significantly affected drug release (P<0.05). Besides the poor aqueous solubility of I, the factors possibly affecting drug release included: (a) the formation of a rate-limiting II gel barrier; (b) the interaction of I with ionized amino groups of II; (c) the effect of electrolyte on the II's gel barrier formation; and/or (d) decreased aqueous solubility of I in the presence of electrolyte.

Chitin↗

PubMed2002

Normal-phase and stability-indicating reversed-phase high-performance liquid chromatographic methods for the determination of the novel antitumor agent: 1-methylpropyl-2-imidazolyldisulfide.

1-Methylpropyl-2-imidazolyl disulfide (MID) is a novel antitumor agent currently in Phase I clinical trials. The chromatographic behavior of MID and its potential impurity, degradation product, and metabolite 2-mercaptoimidazole (2MI) was studied under reversed-phase (RP) and normal-phase (NP) conditions. Both RP- and NP-HPLC separation methods were developed. RP-HPLC was validated as a stability-indicating assay for MID. NP-HPLC retained both MID and 2MI and pending further validation, could prove useful in the study of MID pharmacokinetics.

Antineoplastic Agents↗

PubMed2002

Solubility, ionization, and partitioning behavior of unsymmetrical disulfide compounds: alkyl 2-imidazolyl disulfides.

Alkyl 2-imidazolyl disulfide compounds are novel antitumor agents, one of which is currently being evaluated in Phase I clinical trials. These molecules contain an unsymmetrical disulfide fragment, the lipophilic and electronic contributions of which are still not defined in the literature. Lipophilicity, ionization, and solubility of a number of alkyl 2-imidazolyl disulfides were studied. Based on the additivity of lipophilicity and ionization properties, the contribution of the unsymmetrical disulfide fragment to lipophilicity and ionization was elucidated. The unsymmetrical disulfide fragment contributed a Rekker's hydrophobic constant of 0.761 to the lipophilicity of these compounds and an approximated Hammett constant (sigma) of 0.30 to their ionization. The applicability of the general solubility equation (GSE) proposed by Jain and Yalkowsky in predicting the aqueous solubility of these analogs was evaluated. The GSE correctly ranked the aqueous solubilities of these compounds and estimated their log molar solubilities with an average absolute error of 0.35.

Disulfides↗