Polyethylene Glycol Suppositories Research Articles

Rectal mucosa damage in rabbits after subchronical application of suppository bases.

The effect of suppository bases on rabbit rectal mucosa was investigated using six triglyceride bases, polyethylene glycol, and a triglyceride base combined with monoglycerides or fatty acids and methyl esters of those acids. Rectal irritation was evaluated and scored according to defined pathological features. "Pure" triglycerides and a triglyceride to which a nonionic surfactant was added caused severe mucosal damage with ulceration and inflammation. Hyperemia was characteristic for irritation by polyethylene glycol suppositories. Mucosal damage by a pure triglyceride combined with monoglycerides or fatty acids and methyl esters of those acids was similar but statistically less pronounced than with all other bases.

In-vitro release of diazepam from conventional and double-layer polyethylene glycol suppositories

AbstractA dissolution cell of simple design has been devised specifically for the assessment of hydrophilic suppositories. The measured total percentage release of three conventional diazepam formulations has been measured and interpreted in terms of appropriate kinetic microconstants. The desirability of assessing such tests in terms of a dissolution half-life is discussed.A novel hydrophilic double-layer suppository has been formulated and its measured dissolution profile is described both mechanistically and in terms of suitably derived kinetic equations. The initial total percentage release of this formulation was significantly greater than that of the conventional suppositories which were tested. It is suggested that a double-layer suppository of this type could be therapeutically advantageous in the treatment of epilepsy.

Influence of Adjuvants of Polyethylene Glycol Suppositories on the Physical Characteristics and Drug Bioavailability in Rabbits

AbstractTheophylline suppositories were made by the fusion method, using a polyethylene glycol base. Formulations were prepared containing theophylline in the plain base, and in base with added sodium salicylate or lecithin-sodium deoxycholate as adjuvants. Changes in melting range over time were studied. Differential scanning calorimetry studies characterized the physical nature of the formulations as being brittle or elastic. These data were confirmed by concurrently measuring the initial slope of stress -strain curves obtained at constant strain rate during hardness determination. Release rates were determined with a modified dissolution basket containing glass beads and dialyzing membrane. It was found that drug release rate from plain suppository base > base containing lecithin-sodium deoxycholate > base with sodium salicylate. In vivo bioavailability of theophylline after rectal administration in rabbits showed that rectal absorption was not enhanced in the presence of adjuvants, and theophylline wa...

Intravaginal administration of RU 486 in humans and rats: inadequate absorption in humans

Vaginal absorption of the antiprogesterone steroid RU 486 was studied in humans and rats. In rats, RU 486 was sufficiently absorbed to terminate early pregnancy following vaginal, oral or intramuscular administration. The quantitation of RU 486 in serum showed that the ratios of the areas under the concentration curves per mg administered were 1:2.8:3.4 for the vaginal, intramuscular and oral routes, respectively. Female volunteers received RU 486 vaginally in polyethylene glycol (PEG) suppositories, in tampons and in oil solution. Following vaginal (PEG-suppository) and oral administration of 100 mg of RU 486, the ratio of the areas under the serum concentration curves was 1:56, respectively. From tampons and oil, RU 486 was absorbed in a similar manner to that of the PEG-suppositories, resulting in nanomolar serum concentrations. In humans no biological effects were noted following vaginal administration of RU 486. These data suggest that vaginal release of RU 486 is not a successful route of administration in humans.

Bioequivalence and Pharmacokinetic Profile of Promethazine Hydrochloride Suppositories in Humans

A bioequivalence study of promethazine hydrochloride (10-[2-(dimethylamino)propyl]-phenothiazine monohydrochloride) was conducted in 20 male human subjects with the purpose of comparing, under blind condition, the human serum levels of promethazine in three different formulations. The formulations tested were a 50-mg promethazine hydrochloride polyethylene glycol suppository, a 50-mg promethazine hydrochloride cocoa butter-white wax suppository, and a 50-mg oral dose of promethazine hydrochloride syrup. Each subject received single doses of each of the three formulations on each of three different days on a crossover basis. From the measured serum levels, estimates of the bioavailability parameters (area under the serum concentration versus time curve, time-to-peak serum concentration, and peak serum concentration) were obtained by least-squares digital computer fitting. Also, a one-compartment pharmacokinetic open model with two consecutive first-order input steps is proposed. Statistical analysis of the results was performed by using a linear multiple regression approach for the analysis of variance. No significant differences between the syrup and the polyethylene glycol suppositories were obtained (p>0.05) for the above three bioavailability parameters. However, the polyethylene glycol suppositories provided statistically higher peak serum concentration, shorter time-to-peak serum concentration, and larger area under the serum concentration versus time curve than the cocoa butter-white wax suppositories.

Dissolution of Suppositories V: Influence of Aging on Aspirin Release from Polyethyleneglycol Suppositories with and Without Crospovidone

AbstractThis report details the effect of aging on release of aspirin from four PEG blends containing crospovidone as a disintegrant in concentrations of 0, 0.5, 1 and 5%. It has been reported in the literature that release from suppository formulations is often altered upon aging. In this experiment, suppositories containing 350 mg aspirin were dissolved in 1,000 mls of pH 8.0 dissolution fluid, at 37.5° with an agitation rate of 50 rpm. Suppositories were designated as fresh (less than 10 days old), 4 months old and 6 months old. Aspirin was assayed at 265 nm. Dissolution profiles as well as dissolution half-times were reported. Aging had little effect on Base A and Base B. However, Ease C exhibited an ambiguous effect in that the dissolution half-times were inconsistent. Base D exhibited a dramatic change in release upon aging in that the dissolution half-times increased from 23 minutes to 55 minutes with 1/22 crospovidone. It is hypothesized that Base D stabilized when larger amounts of crospovidone a...

Calorimetric study as a tool on preparation of polyethylene glycol suppositories

Through DSC and DDSC approach some findings in molecular pharmaceutics concepts of PEO suppositories were confirmed. It was stated that the cooling rate of solidification, core-crust location in suppository and aging, influence the nature of PEO 4000 structure.

院内製剤をめざした塩酸プラゾシン座剤の調製 放出およびバイオアベイラビリティ試験による基剤の選択

For use in hypertensive emergency, 2 types of prazosin hydrochloride (PRZ) suppositories were prepared with Witepsol H-15 and polyethylene glycol (PEG) as typical lipophilic and hydrophilic bases respectively. The suppositories were used for in vitro release and in vivo bioavailabilityIn in vitro test, the Witepsol suppository released slowly 80% of PRZ content for 5 hr. The release rate of PRZ from the PEG suppository was rapid compared to that from the Witepsol suppository (almost 100% for 2.5 hr).Contrary to the in vitro release, PRZ plasma concentration curves in rabbits for the Witepsol suppository showed better absorption profile than for the PEG suppository, suggesting higher clinical applicability of the Witepsol suppository. It was also emphasized that in vivo bioavailability test is essential for selection of suitable suppository base from those of which physicochemical properties widely differ.

Rectal absorption of metronidazole from polyethylene glycol suppositories.

The rectal absorption of metronidazole from an aqueous suspension, a fatty suppository and three different polyethylene glycol suppositories was studied in healthy volunteers and compared with absorption from an oral solution. Rectal absorption was found to be rather slow for all suppositories. Of all rectal dosage forms, the polyethylene glycol suppositories gave the highest peak plasma levels and the highest relative bioavailability. Compared with oral administration, a relative bioavailability of 80% could be obtained.

Gas Liquid Chromatographic Determination of Promethazine Hydrochloride in Polyethylene Glycol Suppositories Using the Hall's Electrolytic Conductivity Detector

Abstract A gas liquid chromatographic method using the Hall's electrolytic conductivity detector is described for the determination of promethazine hydrochloride in polyethylene glycol suppositories. This method is capable of distinguishing the intact drug from its thermal degradation products. A linear relationship between peak height ratio (promethazine/promazine) and promethazine hydrochloride concentration is found up to a concentration of 600 μg/ml. In the presence and absence of polyethylene glycol vehicle the recovery of promethazine hydrochloride is found to be 100.2 and 99.7 percent respectively. The percent coefficient of variation is 0.62 and 0.94 in the absence and presence of polyethylene glycol vehicle.

Correlations between Physical and Drug Release Characteristics of Polyethylene Glycol Suppositories

The mechanical strength and elastic moduli of blocks of polyethylene glycol with a range of molecular weights were determined. A rotating‐basket dissolution test was used to measure the release characteristics of prednisolone from similar blocks. The effects of blending bases of different molecular weight and of the addition of water also were determined. Linear relationships were found for the mechanical strength, molecular weight, and release rate, but no simple relationship could be observed for the elastic moduli.

Salicylate Release Characteristics of Selected Polyethylene Glycol Suppositories

Salicylate suppositories were prepared using polyethylene glycol 1540 and polyethylene glycol 6000 in various proportions. The in vitro release of salicylates from each suppository combination was studied using a closed system apparatus designed to circulate fluid about the suppository at 37 ± 0.2°. At scheduled time intervals, samples of the circulating fluid were assayed spectro‐photometrically for salicylate content. Suppositories were also removed from the apparatus, their length and diameter were measured with a vernier caliper, and the change in their surface area was calculated. These surface area changes were then correlated with the salicylate release data. Release of salicylate from the polyethylene glycol suppositories simulated zero‐order kinetics, and the time for 50% release of salicylate (t½) from each polyethylene glycol combination did not differ significantly for salicylic acid or its sodium salt. Salicylate release differed markedly for bases composed solely of polyethylene glycol 1540 or 6000; however, when suppositories contained a mixture of the two polyethylene glycols, the rate of release of salicylate approximated that observed for a base composed solely of polyethylene glycol 6000.