Rectal Administration Of Suppositories Research Articles

Influence of the dissolution medium on the release of dehydroepiandrosterone from lipophilic suppositories

Abstract Suppositories with cocoa butter containing dehydroepiandrosterone (DHEA) without and with the addition of Span 80 and Tween 80 as surfactants with low and high HLB values were prepared. The physical properties and the drug content of all prepared suppositories were in accordance with the pharmacopoeial requirements. The release study tests in three dissolution media such as water, lactic acid solution at pH 4.2 and phosphate buffer at pH 7.4 were carried out. In acidic and alkalic media only about 10% and 27% of DHEA were released, respectively. The addition of Span 80 to the suppository mass did not improve the release process, but the addition of Tween 80 caused the increase in the amount of DHEA released in the acidic medium to about 35%. The data showed that rectal administration of suppositories with DHEA based on cocoa butter caused about 30% availability and after vaginal administration, only topical activity can be expected. By the addition of Tween 80 to the suppository mass availability of DHEA of about 35% from vaginal suppositories can be achieved.

Improvement of availability of allopurinol from pharmaceutical dosage forms I - suppositories

Solid dispersion and crystallization of a very slightly water-soluble drug, allopurinol, were prepared using urea, sodium salicylate and β-cyclodextrin ( β-CD) as carriers. The spectroscopic infra-red (IR), differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) data indicate a role of these carriers in decreasing the crystallinity of allopurinol and complexing abilities. Solid dispersion and crystallization of the drug with these carriers were used in suppository formulations to investigate their role in enhancement of drug release through the membrane barrier. The bases used included Suppocire AM and the mixture of polyethylene glycols (PEGs). The release rates of allopurinol from lipophilic and hydrophilic suppository bases were examined and compared with those obtained for their inclusion compounds incorporated in the same bases. The prepared suppositories were evaluated for in-vitro drug release, when fresh and on storage. The release of pure allopurinol from the lipophilic base was remarkably higher than that from the hydrophilic one. The release of allopurinol from lipophilic as well as hydrophilic bases was significantly enhanced by crystallization of the drug from 5% w/v of sodium salicylate. Allopurinol crystallized from sodium salicylate, showed enhanced release reaching about 100% in 1 h from the Suppocire AM base. The obtained data from these experiments proved the superiority of the PEG formulations containing coevaporates of the drug to sodium salicylate, ratio 1:1, or of the drug to β-CD, ratio 1:2; T 90%,12 and 36 min, respectively. A significant decrease of uric acid excretion in rabbits was observed after rectal administration of suppositories containing allopurinol crystallized from sodium salicylate.

Preparation and utility of glibenclamide suppository for hospital use

Glibenclamide (GC) is widely used as an oral hypoglycemic drug in the treatment of non-insulin dependent diabetes mellitus (NIDDM). Since GC is usually taken for a long period, side effects and noncompliance are among the problems. In order to solve those problems, we prepared GC suppositories and examined their usefulness. Suppositories containing 4, 20, and 40 mg of GC were prepared and examined for drug release, drug absorption and blood glucose levels after the rectal administration of suppositories in rabbits. In the release test, GC suppositories released the drug continuously for 6 hours. The areas under the drug release time curve (ADT) of 20 and 40 mg GC suppositories were 3.5 and 6.2 times of 4 mg GC suppositories respectively. The plasma concentrations after administration of 4 and 20 mg GC suppositories showed about the same profiles for 6 hours. After administration of 40 mg GC suppositories, the maximum plasma concentration (Cmax) was observed at 2 hours. All the GC suppositories showed lower blood glucose levels compared with the control. The remainder of the area under the blood glucose concentration time curve between the control (RAUC) in the case of 40 mg GC suppository was 1.3 times larger than that of the 4 mg GC suppository. The GC suppositories sufficiently lowered the blood glucose levels. These results suggest that the GC suppositories should be useful in the hospital preparation for the treatment of NIDDM patients.

Anorectal stenosis in patients with prolonged use of suppositories containing paracetamol and acetylsalicylic acid.

We report five cases in which anorectal stenosis was associated with chronic administration of suppositories containing paracetamol and acetylsalicylic acid. All patients were females taking suppositories for chronic migraine. Patients experienced anal pain, tenesmus, fecal incontinence, and, in two cases, intestinal obstruction. Lesions were characterized by a severe circular narrowing of the distal rectum with superficial ulcerations. Radiographs demonstrated the presence of sinus-tract-like formations in the diseased segment and thickening of the rectal wall. Histologic examination showed signs of chronic inflammation with deep ulcerations associated with obliteration of the lamina propria by a fibromuscular proliferation, as was described in the solitary ulcer syndrome of the rectum. Rectal administration of suppositories was discontinued in all the patients. Two patients were improved by anorectal dilatation, but the remaining three required a left proctocolectomy with subsequent coloanal anastomosis. The use of such suppositories must be restricted.

Influence of the Hydrophilicity of Suppository Bases on Rectal Absorption of Carprofen, a Lipophilic Nonsteroidal Anti-Inflammatory Drug

The influence of the hydrophilicity of fatty suppository bases on the rectal absorption of the lipophilic drug carprofen (octanol–buffer, pH 7.4; partition coefficient, 40) was investigated in dogs. Five animals received each of six carprofen formulations in a random sequence: intravenous, oral, and rectal solutions, and three suppository formulations. The suppository vehicles tested were semisynthetic glycerides containing saturated fatty acids mainly in the range of C10 to C18 [Massa Estarinum A (MEA), Massa Estarinum B (MEB), and Massa Estarinum 299 (ME299)]; their hydroxyl values increased from 1 for ME299, through 24 for MEB, to 45 for MEA. Following every drug administration, blood samples were collected over a period of 104 h and carprofen plasma concentrations were measured by a specific HPLC method with UV detection. The rate and extent of carprofen absorption were characterized by evaluation of the maximum plasma concentrations (Cmax), the time of their occurrence (tmax), absolute bioavailabilities, statistical moments, and by deconvolution. Carprofen was rapidly and completely absorbed from the oral solution. The maximum concentrations obtained with oral solutions were significantly higher than those observed with rectal solutions and with the three suppository formulations. Results obtained with the rectal solution exhibited a high degree of intersubject variability. After rectal administration of suppositories, the rate and extent of carprofen absorption increased with the hydroxyl value of the suppository base; the mean absorption times (MAT) and tmax were shorter with MEA (2.15 and 1.7 h, respectively) than with the less hydrophilic vehicles (MEB: 4.09 and 2.1 h, respectively; ME299: 4.22 and 2.4 h, respectively). The mean plasma concentrations of carprofen observed after rectal administration rose with increasing hydrophilicity of the suppository base. On the other hand, Cmax and partial areas under the curves from 0 to 8 h after administration of the lipophilic ME299 were lower (21.2 mg/L and 119.1 h · mg/L, respectively) than those obtained with the other, more hydrophilic suppository formulations (MEB: 27.0 mg/L and 152.1 h · mg/L, respectively; MEA: 30 mg/L and 171.8 h · mg/L, respectively). Fractions of the dose of carprofen absorbed from the suppository vehicle ME299 (0.53) during the 6 h following drug administration were lower than those absorbed from vehicles MEB (0.69) and MEA (0.72).

Improvement by adjuvants on the rectal bioavailability of non-absorbable drugs following administration of suppository.

The influence of suppository bases and adjuvants on the release rate of drugs and the absorption of non-absorbable drugs such as sulfanilic acid (SA) and sulfaguanidine (SG), was investigated following the rectal administration of suppositories. The suppository bases used were lipophilic bases such as Witepsol W 35, H 15, S 55, E 75 and hydrophilic base such as macrogol. SA was rapidly released from macrogol, W 35, H 15 and S 55, except E 75. On the other hand, SG was rapidly released from macrogol, whereas the release of SG from lipophilic bases was slow. Rectal absorption of SA and SG following administration of each drug alone in suppository form was slight. On the addition of diclofenac sodium (DF) as absorption promoter the blood levels of SA and SG released from all suppositories increased by about two to four fold compared with those suppositories containing only SA or SG, respectively. However, the absorption of SG still did not attain sufficient levels by the administration of DF only. The rectal absorption of SG was markedly increased by the release rate of the drug from the suppository. These results indicate that after administration of these suppositories the bioavailability of non-absorbable drugs was sufficiently improved by enhancing both the release rate from the suppositories and the rectal membrane permeability.

Enhanced absorption of phenobarbital from suppositories containing amino acid and choline salts of phenobarbital.

Dissolution and permeation patterns of phenobarbital (PB) from basic amino acid and choline salts of PB indicated that drug dissolution from the salts was faster than that of PB itself. Release of the drug from Vosco H15 suppositories containing the salts was faster than that from the suppository containing PB itself. After rectal administration of suppositories containing the salts to rabbits, the blood levels were significantly (p < 0.05) higher than those following administration of the suppository containing PB itself during a period from 30 min to 2 h.

Pharmaceutical evaluation of hollow type suppositories. IV. Improvement of bioavailability of propranolol in rabbits after rectal administration.

Three kinds of suppositories were constructed with oleaginous base material (Witepsol H-15): a conventional type suppository containing propranolol (PPL) hydrochloride mixed with a base material (I), a hollow type suppository containing PPL in a form of aqueous solution (PPL was dissolved in isotonic NaCl solution) in its cavity (II), a hollow type suppository containing PPL as powder (hydrochloride salt) in its cavity (III). Bioavailability was estimated after rectal administration of each suppository in rabbits and compared with oral administration. The peak plasma PPL concentration (Cmax) and the area under the plasma concentration-time curve (AUC) were lower with I than with II or III. The Cmax and the AUC measured after rectal administration of III were significantly higher than those in the case of oral administration. By using III, the highest values of the mean Cmax (795 +/- 160 ng/ml) and of the mean AUC (459 +/- 21 h X ng/ml) were obtained. It was found that systemic availability was increased by rectal administration of PPL hollow type suppositories. These data on bioavailability suggested that PPL was absorbed more efficiently with the hollow type suppository than with the conventional one. PPL was released faster from II and III than from I. It was concluded that the hollow type suppository was a suitable device for absorption of PPL into the rectum.