Biomedical subjects

H V Maulding

Publications and source records attributed to H V Maulding.

At least 19 recordsLinked to original sources

PubMed1988

Effect of particle size on the in vitro and in vivo degradation rates of poly(DL-lactide-co-glycolide) microcapsules.

Three different sieve size fractions of ergot-containing biodegradable microcapsules were examined both in vitro and in vivo. The sieve sizes and average particle diameter, (micron), were: less than 45-75 (mean = 30); 75-106 (mean = 79); 106-177 (mean = 130). These microcapsules contained ca. 9% drug and were produced from 50:50 poly(DL-lactide-co-glycolide). The objective was to determine the effect of particle size on in vivo and in vitro degradation rates. The microcapsules were injected into rat gastrocnemius muscle and excised and examined at various time points up to 70 days. Initially a minimal tissue response was noted which was characterized by a sharply localized acute inflammatory reaction. Following this, connective tissue and foreign body giant cells engulfed the microcapsules at 20-30 days. Only vestiges of the microcapsules were found surrounded by minimal connective tissue and foreign body giant cells after 60-70 days. The tissue reaction was a minimal, sharply localized foreign body giant cell and connective tissue process for all three size groups of microcapsules. The largest microcapsules (mean = 130 microns) exhibited a slightly greater tendency to undergo in vivo and in vitro degradation relative to the other groups. However, it can be concluded that over the microcapsule size ranges examined minimal differences in the degradation properties of the polymeric matrices and consequently those of the microcapsules were noted.

Animals↗

PubMed1985

Biodegradation of and tissue reaction to 50:50 poly(DL-lactide-co-glycolide) microcapsules.

The biodegradation of the copolymer 50:50 poly(DL-lactide-co-glycolide)-lypressin microcapsules was studied by light and electron microscopic methods and 14C release. Intramuscular injection sites of microcapsules in rats were studied by dissecting and conventional light microscopy as well as scanning (SEM) and transmission electron microscopy. A minimal localized acute myositis was seen initially at the injection sites. By Day 4, a few small foreign body giant cells were present participating in the minimal foreign body response. Later the inflammatory cells decreased and the individual microcapsules were walled off by immature fibrous connective tissue and large syncytial foreign body giant cells. By Day 35, definitive changes in some microcapsules, consisting of a granular and slightly eroded appearance of the internal matrix, were seen by SEM. By Day 42, the outer rims of the microcapsules were extensively eroded. At Day 56, the inflammatory and connective tissue reactions were almost completely resolved and biodegradation continued so that only remnant pieces of the microcapsules were present at Day 63. The morphologic picture correlated well with loss of 14C radioactivity, which could no longer be detected at the injection sites on Day 56. Phagocytosis did not seem to be an important factor in the biodegradation.

Animals↗

PubMed1978

Solid-state dispersions employing urethan.

The dissolution rates of a number of drug-urethan solid-state dispersion systems were studied. A marked enhancement of the initial dissolution rates of several poorly water-soluble drugs was found when they were incorporated into a urethan matrix by heat fusion. These differences were considerable when pure substances such as griseofulvin, hydrocortisone, chloramphenicol, and acetaminophen were compared to the urethan-drug solid dispersion. Physical mixtures of the medicinal agents with urethan also gave a marked increase in the amount of drug in solution, with the value in most cases being over one-half that of the solid-state dispersion. Data are given, comparing ultrafiltration with samples filtered through cotton, regarding drug content remaining in solution.

Chloramphenicol↗

PubMed1977

Degradation kinetics of a substituted carbinolamine in aqueous media.

The apparent first-order breakdown of the medicinally active agent 3-(p-chlorophenyl)-2-ethyl-2,3,5,6-tetrahydroimidazo[2,1-b]thiazol-3-ol was studied in aqueous solutions where dehydration gave the unsaturated compound 3-(p-chlorophenyl)-5,6-dihydro-2-ethylimidazo[2,1-b]thiazole. This thiazole was the primary solvolytic product produced in approximately quantitative yields for the temperature range studied and ostensibly underwent no further reaction in acidic media even on prolonged heating. Investigations were carried out at various pH values in standard buffers at constant ionic strength. The ionization constants of the compounds are reported as well as the apparent activation energies for the degradation in acid and acetate buffers. The influence of ionic strength on the velocity constant was determined.

Buffers↗

PubMed1975

Practical kinetics I: Quantitation of barbiturate stability by TLC.

The purpose of this work was the application of established techniques to the quantitation of stability investigations of liquid formulations as well as in solution kinetic studies. The process consists of streaking aliquots of reaction solution on TLC plates, development, elution, and analysis of the substances in the eluate. Several barbiturates were investigated regarding their decomposition at elevated temperatures. Reasonable correlation is noted between obtained rate constants and literature data. This technique represents a utilitarian approach to stability screening of compounds in solution, aqueous or otherwise, where chromatographic separation and analytical methodology for the pure compound are available.

Amobarbital↗

PubMed1975

Practical kinetics II: quantitation of procaine stability by TLC.

This work illustrates further application of TLC as a tool in kinetic investigations of organic molecules. The procedure consists of: (a) streaking or spotting a known volume of reaction solution on thin-layer plates, (b) developing the plates, (c) eluting the compound under study from the adsorbent, and (d) assaying the material in solution. Procaine was examined regarding its hydrolysis at above ambient temperatures. The reaction was monitored spectrally and by the TLC technique. Velocity constants derived by the two methods were similar in value. Rate constants obtained from procaine samples eluted from silica gel plates following development were in good agreement with those previously reported in the literature.

Buffers↗

PubMed1975

Practical kinetics III: benzodiazepine hydrolysis.

The velocity constants for chlordiazepoxide hydrolysis were measured by independent techniques. A quantitative TLC kinetic procedure is compared with an extractive method. The data derived from both processes are in approximate agreement, further exemplifying the feasibility of TLC for rapid stability evaluation of liquid formulations as well as solution kinetic studies. In the extractive procedure, benzodiazepine-substrate was separated from the lactam product by methylene chloride extraction of acidic aqueous solution. The TLC procedure consisted of separation on silica gel plates followed by elution and subsequent analysis. The log kappa-pH relationship for the hydrolysis representing water addition coupled with expulsion of methylamine is presented. This function is characterized by water and hydroxide-ion attack on monoprotic species along with specific hydrogen-ion catalysis at higher hydronium-ion concentrations, and the rate law for the decomposition of chlordiazepoxide is given. Trhrough several half-times (pH 0.15-11.5, 79.5 degrees), this hydrolytic reaction generating lactam predominated; however, more benzophenone was formed as the pH decreased. Velocity constants were invariant over a 200-fold concentration range. The subsequent acid-facilitated cleavage of lactam to benzophenone was not further investigated. Both general acid catalysis and general base catalysis were evidenced, with borate, acetate, formate, and phosphate buffers accelerating the conversion of chlordiazepoxide to lactam. At pH values below neutrality, nonlinear dependency of the rate constant on buffer concentration was observed. This finding may be explained by a change in the rate-determining step as buffer concentration varied.

Buffers↗

PubMed1975

Alcoholysis of medicinally active 5-aminodibenzo(a,d)cycloheptenes.

The rate constants for alcoholic solvolysis of the hydrochloride salts of diethylaminodibenzo(a,d)cycloheptene and related amino congeners were determined. The objective was a study of the comparative ease of cleavage of the C-N amino linkage by various aliphatic alcohols. The interaction of protonated amines of this series with alcoholic hydroxyls presumably leads to formation of the corresponding ethers in a manner somewhat analogous to alkoxide reaction with alkyl bromides. The methyl ether produced from solvolysis of diethylaminodibenzocycloheptene hydrochloride was isolated and identified. Methanol appears to react somewhat more rapidly with the amine hydrochlorides than other aliphatic alcohols. The latter produce almost invariant velocity constants with a given amine hydrochloride. The exception was tertbutanol, which resulted in Kobs values about one-third of those given by the other alcohols. Some velocity constants in formic and acetic acids were evaluated. Generation of carbonium ions of appreciable lifetime was indicated in formic acid by the formation of a highly colored (red-violet) solution. This color may be a manifestation of the dibenzotropylium ion.

Acetates↗

PubMed1975

Nonisothermal kinetic studies III: rapid nonisothermal-isothermal method for stability prediction.

A continuous nonisothermal-isothermal method for stability prediction was developed. The approach yields all necessary parameters for prediction, including reaction order. The experimental procedure involves changing the temperature of the samples being studied until degradation is rapid enough to proceed at a convenient isothermal rate for a sufficient number of half-lives with adequate analytical sensitivity so that the reaction order can be unambiguously determined. The analytical information obtained during the nonisothermal and isothermal portions of the experiment is utilized without curve matching in calculating the activation energy and determining the reaction order, reaction rate, and stability prediction at any desired temperature. Model experiments include the acid-catalyzed hydrolysis of acetylcholine bromide and the inversion of sucrose.

Acetylcholine↗

PubMed1975

Solvolysis of a substituted imidazoline, mazindol.

Hydrolysis of mazindol to form 2-(2-aminoethyl)-3-(p-chlorophenyl)-3-hydroxyphthalimidine was followed spectro-photometrically in aqueous solutions at temperatures between 37 and 70degree, pH values up to 7.6, and an ionic strength of 0.2. The effects of acetate, formate, and phosphate buffers as well as ionic strength on the observed rate constants were investigated. An interesting nonlinear dependency of the kobs with buffer concentration was noted. The velocity constants declined with increasing hydrogen-ion concentration; the log k-pH profile and rate law are given along with other relevant data.

Buffers↗

PubMed1974