Ethyl acrylate-induced gastric toxicity. II. Structure-toxicity relationships and mechanism

Earlier studies conducted in this laboratory demonstrated that gavage administration of ethyl acrylate caused pronounced gastric toxicity in rats given single or repeated doses. The current studies were undertaken to investigate the structural, metabolic, and physical basis of this chemically induced gastric toxicity. Gavage administration of equimolar doses (2 mmol/kg) of methyl or ethyl acrylate in corn oil resulted in profound gastric toxicity in male F344 rats, while acrylic acid and n-butyl acrylate were without effect. Furthermore, gavage administration of equimolar doses of methyl propionate or ethyl propionate (saturated analogues of methyl acrylate and ethyl acrylate, respectively) as well as methacrylic acid esters were without gastric toxicity. These results indicate that structural requirements for acrylate esters to cause gastric lesions include an intact ester moiety, a double bond, and no substitution at carbon number 2. Additional studies indicate that gastric toxicity may be attributed to the intact ester molecule or to metabolite(s) other than products of carboxylesterase-mediated hydrolysis (acrylic acid and alcohol) and that gastric toxicity is dependent upon both acrylate ester concentration in dose vehicle and the lipophilicity of the dose vehicle (corn oil vs water).     

The chronic toxicity of technical and analytical pentachlorophenol in cattle. I. Clinicopathology

The objectives of this study in female yearling Holstein cattle were to define the toxic effects of (1) long-term exposure to analytical pentachlorophenol (aPCP), and (2) to determine the influence of the contaminants in technical pentachlorophenol (tPCP) in the toxic syndrome. Four groups of three heifers each were exposed for 160 days to aPCP, tPCP, or a mixture thereof in the feed. A fifth group of three animals served as unexposed controls. All treated cattle received the same amount of PCP; 20 mg/kg/day for 42 days which was reduced to 15 mg/kg/day for the remainder of the study because of a suspected decrease in body weight gain in all PCP-exposed animals compared to controls. Fat and liver samples for chemical analyses were collected at the end of the study. Major findings in the tPCP-exposed heifers included a dose-related decrease in body weight, decreased feed efficiency, progressive anemia, a dose-related increase in liver and lung weights, and a decrease in thymus weight. The most conspicuous lesion was market villous hyperplasia of the urinary bladder mucosa in two of three animals exposed to the highest level of tPCP. There were minimal hepatic lesions although hyperplasia of the mucosal lining of the gali bladder and bile duct was noted in some animals exposed to tPCP. Animals exposed to aPCP were, in general, comparable to the controls. Hepatic mixed function oxidases were increased by aPCP, but more so by tPCP. A decrease in thyroxine concentration was found in all PCP-treated cattle. Immunologic studies suggested a progressive tPCP dose-related enhancement in the lymphoproliferative response, an in vitro correlate for cell-mediated immunity. Observed effects on humoral immune parameters were equivocal. The results of this study indicate that toxicity of PCP in cattle is primarily attributable to its contamination with toxic impurities.     

Differential toxicity of trans-permethrin in rainbow trout and mice: I. Role of biotransformation

The trans isomer of [1R,S] permethrin (t-per) was > 110 times more toxic to rainbow trout than to mice by both iv and ip administration. The importance of trans-permethrin biotransformation in this differential toxicity was assessed by measuring rates of t-per biotransformation in trout and mouse tissues in vitro, and the effect of inhibitors of drug metabolism on t-per lethality in both species. A previous study had shown that ester hydrolysis by trout liver, plasma, and kidney is much slower than that seen in these same tissues in mice. The present work further indicates that oxidation of t-per is 35 times slower in trout liver microsomes than mouse microsomes when the tissue suspensions were incubated at the body temperature of trout and mice (12°C for trout and 37°C for mice). Inhibition of esterase activity with tri-o-tolyl phosphate (TOTP) produced no potentiation of t-per lethality in trout while the same compound potentiated t-per lethality at least 1.5-fold in mice. Piperonyl butoxide (PIP) alone produced no potentiation in mice but slightly increased t-per toxicity when administered in conjunction with TOTP. PIP caused a slight increase in t-per lethality in rainbow trout but no increase in t-per lethality from control was observed when trout were pretreated with both TOTP and PIP. When drug metabolism was inhibited, t-per was still 65 times more toxic to trout than to mice. The data indicate that trout, in addition to hydrolyzing t-per slowly, also oxidize the compound considerably slower than mice in vitro. Potentiation of t-per lethality by TOTP suggests ester hydrolysis to be an important t-per detoxification reaction in mice but not in trout. However, since t-per was 65 times more toxic to the trout than mouse when drug metabolism was inhibited, other factors, such as differences in target organ sensitivity may be involved in the differential toxicity of permethrin.     

Effect of administrative vehicle on oral 1,1-dichloroethylene toxicity

The relationship between the acute toxicity and biologic fate of 1,1-dichloroethylene (1,1-DCE) was examined in fasted and fed male Sprague-Dawley rats given 200 mg 1,1-DCE/kg orally in a mineral oil, a corn oil, or an aqueous Tween-80 vehicle. Exhalation of unchanged 1,1-DCE by individual rats was monitored at selected 15-min intervals for 5 hr and all rats were sacrificed at 6 hr. The administrative vehicle affected the magnitude of liver injury in fasted rats; with mineral oil or corn oil, injury was massive [> 100-fold elevation of glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT)] whereas with the aqueous Tween-80 vehicle, injury was moderate t 15-fold elevation of GOT and GPT). In contrast, in all fed groups liver injury was slight (two- to threefold elevation of GOT and GPT). Rats with massive liver injury also had an ～50-fold increase in plasma free hemoglobin and their kidneys exhibited numerous granular “heme” casts in Henle's loop without apparent degenerative changes in either glomeruli or tubular epithelium. No pathologic changes were observed in heart, lungs, spleen, adrenals, or duodenum. The administrative vehicle did not affect the total amount of 1,1-DCE exhaled, which was approximately half the given dose, nor did the vehicle affect the initial rapid phase of 1,1-DCE exhalation, which lasted ～1 hr and had $\text{t}\text{1}\text{2}$ values ranging from 15 to 21 min for the fasted groups and from 10 to 13 min for the fed groups. In contrast, the later slow phase of 1,1-DCE exhalation was predictably affected by the administrative vehicle; $\text{t}\text{1}\text{2}$ values for the fasted and fed groups, respectively, were most prolonged with the poorly absorbed mineral oil vehicle (257 and 280 min), intermediate with the more digestable corn oil vehicle (73 and 103 min), and briefest with the more absorbable aqueous Tween vehicle (22 and 42 min). Further studies are needed to determine if the relative resistance of the fed animals to hepatic injury is due to the capacity of these animals to detoxify 1,1-DCE for a longer duration than the fasted animals.     

Effect of alcohol and aldehyde dehydrogenase inhibitors on the toxicity of 3-nitropropanol in rats

The nitrocompounds 3-nitropropanol (NPOH) and 3-nitropropionic acid (NPA) were shown to be equally toxic when injected intraperitoneally into male Wistar rats. The LD50 for NPOH was 0.58 mmol/kg and for NPA it was 0.56 mmol/kg. NPOH was rapidly metabolized to NPA but this conversion was suppressed by prior administration of ethanol or 4-methylpyrazole to inhibit alcohol dehydrogenase. Administration of ethanol or 4-methylpyrazole before NPOH protected rats from intoxication. However, if the alcohol dehydrogenase inhibitors were given after the nitroalcohol, toxicity still occurred. Administration of the aldehyde dehydrogenase inhibitor diethyldithiocarbamic acid had little effect on the conversion of NPOH to NPA and did not alter the toxicity of NPOH. It was concluded that NPOH and NPA are equally toxic to rats but that NPOH is toxic due to its being rapidly converted to NPA.     

Effect of omeprazole on gastric secretion in H+,K+-ATPase and in pepsinogen-rich cell fractions from rabbit gastric mucosa

In order to study the effects of the substituted benzimidazole omeprazole on gastric secretory functions, parietal cells and chief cells from rabbit gastric mucosa were separated and enriched by density gradient centrifugation in Percoll. H+,K+-ATPase activity, as well as a 100,000 dalton protein, was found to copurify with a cell fraction morphologically characterized as mainly parietal cells (purity approximately 65%), while pepsinogen copurified with a cell fraction morphologically characterized as chief cells (purity approximately 90%). A spontaneous pepsinogen release (9.9 micrograms/mg cell dry wt X 2 hr), unaffected by both atropine and omeprazole, was found in the chief cell fraction. The release was approximately doubled by both carbacholine (4 X 10(-5)M) and dibutyryl cAMP (db-cAMP, 10(-3)M). The cholinergic stimulation was selectively blocked by atropine, while omeprazole had no effect on pepsinogen release induced by either of the secretagogues. On the other hand, omeprazole inhibited both db-cAMP- and histamine-stimulated acid secretion quantified as [14C]aminopyrine (AP) accumulation in the parietal cell fraction. Cimetidine counteracted only acid secretion induced by histamine. These findings indicate that omeprazole has a specific effect on acid secretion, and are consonant with the hypothesis that the effect is due to H+,K+-ATPase inhibition.     

Hepatotoxicity of acetaminophen in neonatal and young rats. I. Age-related changes in susceptibility

The susceptibility of neonatal (11 days) and young rats (19 and 33 days) to acetaminophen-induced hepatic necrosis was examined. Acetaminophen-induced lethality (LD50) was slightly lower in 19-day-old animals (840 mg/kg) compared to 11- and 33-day-old animals (1220 and 1580 mg/kg, respectively). A toxic dose of the drug ( LD20 ) produced elevated serum glutamate-pyruvate transaminase and lactate dehydrogenase activities 20-24 hr after drug administration only in 19- and 33-day-old animals. Serum enzyme elevation was not observed after a toxic dose of acetaminophen ( LD20 or LD50) in 11-day-old rats. Histological evaluation showed that both 19- and 33-day-old rats developed extensive hepatic centrilobular damage, whereas morphological parameters in 11-day-old animals given acetaminophen were not different from controls. It appears that high doses of acetaminophen are lethal to young rats, but that 11-day-old animals are different from 19-day-old and older rats in that the neonatal animals lack susceptibility to the hepatotoxic effects of the drug. Lower susceptibility of the neonatal rat liver to the hepatic effects of two other hepatotoxicants (bromobenzene and tannic acid) was also observed.     

Dose-dependent toxicity of CCl4 in isolated rat hepatocytes and the effects of hepatoprotective treatments.

The temporal and dose-response relationships of the effects of CCl₄ were studied in isolated rat hepatocytes. CCl₄ decreased cell membrane integrity, as measured by the loss of alanine aminotransferase to the medium and the ability to retain intracellular K⁺. CCl₄ altered metabolic activity, as measured by the rate of urea synthesis and the lactate/pyruvate ratio. Addition of the following chemicals—SKF-525A, promethazine, dibenamine (0.1 mm); reduced glutathione (0.25 mm); hexobarbital methionine, cysteine (1 mm)—to the medium did not protect against the toxic effects of CCl₄, although these chemicals have been reported to be hepatoprotective in other experimental models. Incubation at 4°C did protect against CCl₄-induced changes in membrane integrity. These findings suggest that the isolated hepatocyte preparation is a suitable model for demonstrating time and dose-dependent toxic effects. However, they also suggest that there may be differences in mechanism compared with other experimental models.     

Effect of nicotine and caffeine pretreatment on the gastric mucosal damage induced by aspirin, phenylbutazone, and reserpine in rats

The effect of nicotine and caffeine pretreatment by feeding nicotine (2.5 mg %), caffeine (30 mg % base), and their combination (nicotine 2.5 mg % + caffeine 30 mg %) in drinking water ad libitum for 21 days was studied on the gastric mucosal damage induced by aspirin, phenylbutazone, and reserpine in rats. When given alone, neither nicotine nor caffeine produced any visibly discernible gastric lesions. Their concurrent administration too, did not produce any gastric mucosal injury. Pretreatment with nicotine, caffeine, and their combination resulted in significant augmentation of gastric ulcers produced by aspirin, phenylbutazone, and reserpine. However, caffeine administration produced a comparatively less profound augmentation of experimentally induced gastric lesions than that produced by nicotine pretreatment. The enhancement of gastric ulcers in the groups pretreated with the combination of nicotine and caffeine followed by one of the drugs was significantly greater than in the groups treated by either of them alone. The effect of nicotine on the mucus neck cell population of the gastric mucosa and on pancreatic bicarbonate secretion and the gastric secretory effect of caffeine may be responsible for the potentiation of the ulcerogenic effects of aspirin, phenylbutazone, and reserpine.     

Tablet lubricants I. Theory and modes of action

Tablet lubricants are essential components of all tablet formulations, since they prevent sticking of the tablets in the dies. Without tablet lubricants, tablets cannot be produced. A lubricant may be defined as a suitable material, a small amount of which interposed between two rubbing surfaces will reduce friction arising at the interface (Strickland et al., 1960; Komarek, 1967).A lubricant should also be capable of reducing wear on the rubbing surfaces (Silversher, 1969). To perform this function the lubricant must provide a film that will prevent solid-to-solid contact, and is easily sheared (Jentgen, 1971). Lubricants are added to tablet formulations primarily to reduce friction between the die wall and granules as the tablet is formed and ejected (Sprowl, 1974; Lachman et al., 1970). The other main activities attributed to a lubricant are: (a) prevention of sticking of granules to the tooling—anti-adherent; and (b) improvement of granule flow properties—glidant (Lachman et al., 1970). A given lubricant may provide one or more of these actions to varying degrees but no one material is highly efficient in all categories (Sperandeo and De Machi, 1976; Strickland, 1959; Sprowl, 1974). Accordingly combinations of lubricants are often selected to provide the necessary total lubricant effect (Maly, 1963; Munzel and Kogi, 1954). Careful selection is necessary since some lubricants may interact adversely when in combinations; for example, magnesium stearate and talc (De Blaey, 1972), although some authors have found that these two lubricants are compatible (Rubio, 1957; Esnaud et al., 1973). Although tablet lubricants have been used in practice for many decades it is only in the last 15 years that the lubrication process has been studied fundamentally.     

The tensile strength and consolidation of lactose coated with non-ionic surfactants I. Powder

The tensile strength and the resistance to consolidation by pressure or tapping of fine lactose powder coated with increasing amounts of a series of non-ionic surfactants were examined.At a constant packing fraction, both the tensile strength and the resistance to consolidation initially decreased to minima when the coating was monomolecular and then increased as the additive formed pendular bonds between the particles.The packing fraction of the powder after 100 taps increased to a maximum, and then decreased as the amount of the coating material present was increased.Cheng's expression for tensile strength has been used to compare the forces that operate between the particles of the coated and the uncoated powders.     

Development of lipophilic prodrugs of mitomycin C. I. Synthesis and antitumor activity of 1a-N-substituted derivatives with aromatic pro-moiety

Five lipophilic la-N-substituted derivatives of mitomycin C possessing aromatic pro-moieties including benzyl, benzoyl, benzylcarbonyl, benzyloxycarbonyl, and benzoyloxymethyl groups were synthesized, and their physicochemical and biological characteristics were examined. All compounds showed increased octanol/water partition coefficients. lipophilic indexes (k') in HPLC system, and lipid solubilities. Their antimicrobial activities against Escherichia coli B were markedly less than that of mitomycin C except for benzoyloxymethyl mitomycin C. All of the compounds showed significant activity in vivo against P388 or L1210 leukemia system, and especially benzyloxycarbonyl and benzoyloxymethyl mitomycin C showed equal or superior activity to the parent drug at approximately the same low dose area. These results suggested that most of the compounds exhibit their cytotoxicity against tumor cells after being regenerated to their parent drug in the body.     

Enhancement of adriamycin toxicity by carboxymethylcellulose in mice

Carboxymethylcellulose (CMC) (1% in 0.9% NaCl, 0.2 ml/10 g ip) a common suspending agent, enhanced adriamycin (ADR) (15 mg/kg ip) toxicity when administered to mice 5 hr before the antibiotic. Compared with ADR alone, this combination treatment produced, after 7 days, an increase in lethality from 15 to 80%. The pathologic analysis of hearts, livers, kidneys, and small bowels was performed, revealing an increase in the incidence and severity of hepatic damage in mice receiving ADR + CMC. Furthermore, reduced glutathione (GSH) was measured in livers of all mice; the animals treated with CMC and ADR + CMC showed a significant (p less than 0.01) reduction of hepatic GSH in comparison with controls and ADR-alone-treated animals. These data further confirm a crucial protective role for GSH in ADR toxicity and prove that CMC exerts an important biochemical effect on hepatic GSH.     

Enol esters as potential prodrugs I. Stability and enzyme-mediated hydrolysis of α-acetoxystyrene

The stability of α-acetoxystyrene, a model enol ester, was evaluated in aqueous buffered solvents and in human and rat plasma and rat tissue homogenates. The compound was found to be a good substrate for endogenous esterases exhibiting a half-life for hydrolysis in human plasma of <3 min while in phosphate buffer at pH 7.4 and 25°C the calculated t_{$\text{1}\text{2}$} was ~180 h. These results suggest that enol esters may be useful as prodrugs of agents containing an enolizable carbonyl group.     

Renal toxicity of middle distillates of shale oil and petroleum in mice

The tumorigenic potential of middle distillates (JP5, JP8, and diesel fuel marine) of shale oil and petroleum was studied by chronic dermal application on mice. These materials were applied to the backs of young $\text{C}\text{3}\text{Hf}\text{Bd}$ mice three times weekly for 60 weeks. Cyclohexane was used as the vehicle. After 30 weeks of treatment, increased water consumption was observed in all test groups, and increased urine production was seen in many of these groups. Two mice that died in the last week of treatment had severe renal lesions. At the end of the experiment an additional 42 of 336 mice had similar renal lesions. Macroscopically, the characteristic renal lesion consisted of pale, irregular, depressed foci that appeared cuneiform when the kidney was bisected. These lesions appeared to be old infarcts, but microscopically they lacked the usual features of infarction, such as necrosis, hemorrhage, inflammation, and fibrosis. Instead, atrophied and degenerating nephrons supported by an intact reticulum were found. In addition, microscopic examination revealed a high incidence of papillary necrosis. The nature of the lesions suggests that the renal toxicity of these materials is mediated through some type of vascular phenomenon resulting in chronic ischemia. There appeared to be little difference between shale and petroleum-derived distillates (20 vs 24 affected mice, respectively). However, mice treated with shale-derived DFM were most severely affected, and female mice were affected preferentially.     

Biochemical assessment of acute nitrogen dioxide toxicity in rat lung

The early primary biochemical response of lung to NO2 was studied separately from the later secondary responses of inflammation and proliferation by measuring several biochemical parameters in lungs of rats immediately following a 4-hr exposure to nitrogen dioxide (NO2) at concentrations of 10, 20, 30, and 40 ppm. Cell-free lavage fluid contained elevated amounts of lactate dehydrogenase (LDH), malate dehydrogenase (MDH), isocitrate dehydrogenase (IDH), glucose-6-phosphate dehydrogenase (GDH), acid phosphatase (AP), and aryl sulfatase (AS) after 30 or 40 ppm NO2. Total protein and sialic acid were increased in cell-free lavage after 20, 30, or 40 ppm NO2. The amounts of protein, sialic acid, and acid phosphatase recovered by airway lavage were equal to the amounts found in 0.7 ml of plasma, consistent with transudation of this volume of plasma into airways as a source of these parameters. The plasma activity of the other parameters measured was too low to account for their increase in lavage fluid by plasma leakage into airways. Decrease in the number and enzyme content of lavagable cells indicated damage to free cells in the airways. The amount of the decrease in enzyme content of the lavagable cell fraction was similar to the increase in the cell-free lavage for all of the measured enzymes except acid phosphatase, suggesting the release of these enzymes into airways as a result of damage to free cells. However, the LDH isoenzyme profile in cell-free lavage after exposure is inconsistent with free cells as the source of this enzyme. No changes were observed in the whole-lung homogenate content of protein, DNA, lipid, LDH, MDH, IDH, GDH, AP, AS, glutathione reductase, NADPH cytochrome c, or succinate cytochrome c reductase immediately after NO2 exposure. This study indicates that initial acute damage to lung by NO2 results in translocation of enzymes, proteins, and sialic acid into airways. Plasma is a likely source of translocated protein, sialic acid, and acid phosphatase. The sources of the other enzyme activities remain to be identified, with lung parenchyma and free cells as likely sources.     

Trichothecene-induced hemolysis : I. The hemolytic activity of T-2 toxin

In the present investigation, the hemolytic properties of T-2 toxin were examined. Tests with different concentrations of T-2 toxin showed that essentially complete hemolysis of rat erythrocytes commenced after a lag period, the length of which depended on the concentration of toxin. Comparison of the characteristics of hemolysis caused by T-2 toxin, saponins, H2O2, and polyoxyethylene surfactants showed great similarity between T-2 toxin and the latter two which proceed by a free radical mechanism. The same mechanism was suggested for hemolysis caused by T-2 toxin on the basis of the additional following observations: (1) darkness inhibited hemolysis; (2) specific free radical scavengers, i.e., vitamin E, mannitol, and histidine, inhibited hemolysis caused by T-2 toxin.     

Powder flow studies I. Powder consolidation ratio and its relationship to capsule-filling—weight variation

The consolidation of loosely packed powders and powder mixtures in cylindrical containers was studied by applying a series of loads to the surface of the powder bed. The results were plotted as the logarithm of the change in volume versus the logarithm of the applied pressure. The slopes of these plots were similar and the intercepts (consolidation ratio) suggested a relationship to powder flow. The effects of the cylinder diameter and initial height of the powder bed on the powder consolidation ratio were investigated to optimize the method. The application of the powder consolidation ratio to powder flow in hoppers was studied by filling capsules of several formulations on an automatic capsule filling machine. The plots of the coefficient of variation of filled weight versus powder consolidation ratio were linear, indicating a direct relationship between the powder consolidation ratio and capsule-filling—weight variation.     

Toxicity of bis(tri-n-butyltin)oxide in the rat. I. Short-term effects on general parameters and on the endocrine and lymphoid systems

Male and female Wistar rats were fed bis(tri-n-butyltin)oxide (TBTO) at 0, 5, 20, 80, or 320 mg/kg diet for 4 weeks. Clinical signs and decreases in feed and water consumption were observed in the 80 and 320 mg/kg groups. The serum transferase activities (alanine amino transferase and aspartate amino transferase were increased at 20 (males only), 80, and 320 mg/kg. The serum glucose and liver glycogen concentrations were lowered in the 320 mg/kg group. At 80 and 320 mg/kg the serum IgG level was reduced and IgM level was increased. Compared to controls the mean relative weight of the thymus was decreased at 20 (males), 80, and 320 mg/kg. In the groups receiving 80 or 320 mg/kg microcytic anemia was found. The white blood cell counts were decreased, due to the reduction in the number of lymphocytes in the 80 (males) and 320 mg/kg groups. The concentration of neutrophilic granulocytes was increased in the highest dose group. Histopathologic effects included a dose-related lymphocyte depletion of thymic cortex and of T lymphocytes in spleen and mesenteric lymph nodes. In the spleen also depletion of iron stores was found, and in the medullary sinuses of mesenteric lymph nodes, rosettes of erythrocytes were found around mononuclear cells; the occurrence of rosettes increased with dose from 5 to 80 mg/kg, and appeared to be the most sensitive parameter. A low incidence of areas of liver necrosis with inflammatory reaction and bile duct hyperplasia was found in the 320 mg/kg group. A viral or bacterial etiology could be demonstrated for these liver lesions, but they appeared associated with TBTO-induced ulcerative inflammation of the common bile duct as shown in an additional study. In 6-week studies exposure of male weanlings to the 0, 20, and 80 mg/kg diets, the serum insulin concentration in the treated groups was decreased, although the response to glucose challenge was unaffected. The serum thyroxin and thyrotropin (TSH) concentrations were reduced, whereas the luteinizing hormone (LH) concentration was increased in the 80 mg/kg group. The concentrations of follicle-stimulating hormone (FSH) and corticosterone were not changed. The release of LH and FSH was enhanced in the 80 mg/kg group and a tendency toward reduced release was found for TSH. Using immunocytochemistry a dose-related reduction was found in the number and staining intensity of TSH-producing cells in the pituitary, correlating with histopathologically decreased activity of the thyroid.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmaceutical suspension studies I. A comparison of adsorption of polyvinylalcohol at the diloxanide furoate B.P. and polystyrene latex-water interface

The adsorption of a series of polyvinylalcohol fractions onto two solid substrates has been investigated. Using diloxanide furoate B.P. as the adsorbent, adsorption of small molecular weight fractions within pores has been demonstrated. Such adsorption was not observed when using polystyrene latex as the substrate but larger equilibrium quantities were adsorbed onto this surface than onto the drug. The differences in the maximum amount of polymer adsorbed at both solid-solution interfaces have been ascribed to the different hydrophobicities of the surfaces as determined by contact angle measurements.