Polyethylene Glycol Suppositories Research Articles

Rectal bioavailability of amoxicillin sodium in rabbits: Effects of suppository base and drug dose

In this paper, rectal absorption and tissue tolerance of amoxicillin sodium (AS) suppositories prepared in a hydrophilic base, polyethylene glycol (PEG) or lipophilic base, Suppocire® NA 15 (SNA 15), were investigated. Following in vitro characterization, including drug distribution in the suppository bases, drug-base interactions and drug release, pharmacokinetics were investigated in rabbits to determine absolute bioavailability (F) at two dose levels (100 mg and 200 mg). Both types of suppositories were found uniform in weight and content. Powder X-ray diffraction (XRD) and differential scanning calorimetry indicated that AS existed as solid dispersion or anhydrous crystalline dispersion in both suppositories at different ratios without changing melting points of the bases. This was supported by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy conjugated with energy dispersive X-ray (SEM/EDX). In dissolution medium, melting and spreading of SNA 15 and dissolution of PEG suppositories accounted for their different drug release kinetics and mean dissolution time (MDT). A rapid and complete amoxicillin absorption (F close to 100%) with a double peak pharmacokinetic profile was observed alongside minimal signs of tissue irritation in rabbits treated with SNA 15 suppositories at both dose levels. In contrast, the F of amoxicillin from PEG suppositories was 59%, increasing to 77.3% as AS dose doubled from 100 mg to 200 mg, reflected in the slower release predominately controlled by erosion of the base. An in vitro – in vivo correlation was observed (MDT vs F; p < 0.01). AS was stable in SNA 15 suppositories at least for three months at 20 ± 0.2 °C. This research highlighted the advantages of SNA 15 suppositories over the PEG suppositories in providing rapid and complete rectal absorption of AS and tissue compatibility.

P-056. Profound changes in hemodynamics proving late-onset PE being of maternal origin

In this paper, rectal absorption and tissue tolerance of amoxicillin sodium (AS) suppositories prepared in a hydrophilic base, polyethylene glycol (PEG) or lipophilic base, Suppocire® NA 15 (SNA 15), were investigated. Following in vitro characterization, including drug distribution in the suppository bases, drug-base interactions and drug release, pharmacokinetics were investigated in rabbits to determine absolute bioavailability (F) at two dose levels (100 mg and 200 mg). Both types of suppositories were found uniform in weight and content. Powder X-ray diffraction (XRD) and differential scanning calorimetry indicated that AS existed as solid dispersion or anhydrous crystalline dispersion in both suppositories at different ratios without changing melting points of the bases. This was supported by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy conjugated with energy dispersive X-ray (SEM/EDX). In dissolution medium, melting and spreading of SNA 15 and dissolution of PEG suppositories accounted for their different drug release kinetics and mean dissolution time (MDT). A rapid and complete amoxicillin absorption (F close to 100%) with a double peak pharmacokinetic profile was observed alongside minimal signs of tissue irritation in rabbits treated with SNA 15 suppositories at both dose levels. In contrast, the F of amoxicillin from PEG suppositories was 59%, increasing to 77.3% as AS dose doubled from 100 mg to 200 mg, reflected in the slower release predominately controlled by erosion of the base. An in vitro – in vivo correlation was observed (MDT vs F; p < 0.01). AS was stable in SNA 15 suppositories at least for three months at 20 ± 0.2 °C. This research highlighted the advantages of SNA 15 suppositories over the PEG suppositories in providing rapid and complete rectal absorption of AS and tissue compatibility.

Vaginal suppositories of cumin seeds essential oil for treatment of vaginal candidiasis: Formulation, in vitro, in vivo, and clinical evaluation

Fungal infections by resistant Candida species continue to be a significant health problem. Novel antifungal agents such as essential oils of cumin seeds (EOCS) are tested against vulvovaginal candidiasis (VVC). The aim of this study was to develop coated polyethylene glycol (PEG) vaginal suppositories containing EOCS for treatment of VVC. PEG suppositories containing EOCS were prepared ppearance, weight variation, drug content, hardness, dissolution time, release, stability and anticandida activity were evaluated. Biocompatibility of selected formulation was tested in female rabbits, followed by clinical evaluation. Coated suppositories showed complete release of the oil after 30 min, in vitro anti-candida activity, enhanced stability and sufficient safety on the vaginal tissues of rabbits. Clinical results showed significant lower rates of vaginal itching, discharge and dyspareunia combined with negative cultures in 70% of patients, revealing efficacy of EOCS-containing vaginal suppositories for treatment of VVC.

Characterisation of rectal amoxicillin (RAMOX) for the treatment of pneumonia in children

Access to medicines, including their availability and affordability, is a major public health challenge worldwide. This research aimed to characterise rectal formulations containing amoxicillin for the treatment of pneumonia in children under five, as an accessible alternative to existing formulations. Lipophilic Suppocire (S-NA15) and hydrophilic polyethylene glycol (PEG; 80% PEG 1500 and 20% PEG 4000, w/w) suppositories containing 250 mg amoxicillin were prepared. Hardness, apparent viscosity, uniformity of mass, uniformity of content, disintegration and dissolution time were determined. Irritation potential was screened using a slug mucosal assay and antibacterial efficacy against Staphylococcus aureus determined by isothermal microcalorimetry. Both lipophilic and hydrophilic formulations met the European Pharmacopoeia standards for suppositories when tested in vitro. They disintegrated within 30 min with rapid amoxicillin release profiles (98.6 ± 0.9%, 94.9 ± 1.2% over 30 min, respectively). Over-encapsulation of S-NA15 suppositories with hydroxypropyl methylcellulose shells slowed drug release and improved stability over 2 months. S-NA15 suppositories were classified as non-irritant and PEG suppositories only mildly irritant. Antibacterial efficacy of formulations was equivalent to amoxicillin alone. Both PEG and over-encapsulated S-NA15 rectal formulations developed in the present work have shown promise based on pre-clinical screening, and further development is justified to develop a product with commercial potential.

Formulation, Physiochemical, and Microbial Assay of Henna Oil Vaginal Suppository Formulated with Polyethylene Glycol Bases.

Background: Persian Medicine is one of the oldest and richest complementary and alternative options in the field of medicine and has a comprehensive medical system. Henna oil is recommended in Persian Medicine for the treatment of numerous women’s diseases such as cervicitis. To date, henna has been used for many medical purposes, including astringent, bleeding, cardioinhibitory, hypotension, and relaxation. Accordingly, the present study aimed to provide the formulation of a henna-oil-based vaginal suppository and examine its physicochemical and antimicrobial properties. Methods: The present study was approved and performed in accordance with the regulations of Research Council, Kerman University of Medical Sciences, Kerman, Iran, in July 2016. Different percentages of henna oil, glycerin, and gelatin, as well as henna oil and polyethylene glycol 400 and 4000, were mixed to achieve a formulation with proper appearance features and, particularly, without any oil leakage from the suppository surface. Uniformity of weight, uniformity of content, disintegration time, and dissolution test of the suppositories were evaluated. The growth-inhibiting activity of the suppositories and aqueous extract of henna was evaluated against bacteria, including the Gram-positive bacterium Gardnerella vaginalis, Neisseria gonorrhoeae, and group B streptococcus. Results: The formulations had a smooth appearance without any cracks or fractures. Disintegration times for glycero-gelatin and polyethylene glycol suppositories were 60 and 10 min, respectively. 40% of the drug was released from polyethylene glycol suppositories after 60 min, but glycero-gelatin suppositories had no release after three hours. Minimum inhibitory concentration (MIC) of suppositories and aqueous extract were 0.4 mg/mL and 0.01 mg/mL, respectively. Conclusion: Polyethylene glycol suppositories had acceptable physicochemical properties, and the henna extract and suppositories inhibited the three studied pathogens.

Suppository formulations as a potential treatment for nephropathic cystinosis

Nephropathic cystinosis is a rare autosomal recessive disease characterised by raised lysosomal levels of cystine in the cells of all the organs. It is treated by the 6-h oral administration of the aminothiol, cysteamine, which has an offensive taste and smell. In an attempt to reduce this frequency and improve the treatment, cysteamine-containing polyethylene glycol suppositories were prepared and evaluated for dissolution and stability. The results demonstrated that cysteamine release was complete after 30 min, and that there was a uniform drug distribution within the formulations. Twelve-month stability tests highlighted a potential incompatibility among some excipients, although stability was demonstrated for the cysteamine suppositories up to 6 months. These suppositories may provide a useful alternative to the current oral therapy for cystinosis.

Screening paediatric rectal forms of azithromycin as an alternative to oral or injectable treatment.

The aim of this study was to identify a candidate formulation for further development of a home or near-home administrable paediatric rectal form of a broad-spectrum antibiotic - specially intended for (emergency) use in tropical rural settings, in particular for children who cannot take medications orally and far from health facilities where injectable treatments can be given. Azithromycin, a broad-spectrum macrolide used orally or intravenously for the treatment of respiratory tract, skin and soft tissue infections, was selected because of its pharmacokinetic and therapeutic properties. Azithromycin in vitro solubility and stability in physiologically relevant conditions were studied. Various pharmaceutical forms, i.e. rectal suspension, two different rectal gels, polyethylene glycol (PEG) suppository and hard gelatin capsule (HGC) were assessed for in vitro dissolution and in vivo bioavailability in the rabbit. Azithromycin PEG suppository appears to be a promising candidate.

Formulation of Tinidazole Rectal Suppositories

Tinidazole was prepared as a suppository dosage form that could be used rectally in an attempt to render the drug available systemically by a route other than oral route, thus overcoming the side effects of the drug on the gastrointestinal tract. Also such dosage form could replace the intravenous administration whenever it is inconvenient.The influence of the type of suppository base and added surfactants on the physical properties and drug release was studied using lipophilic bases (witepsole H-15, witepsole H-35) and water soluble bases [mixtures of polyethylene glycols PEG 6000:400:200 (30:35:35) and PEG 4000:1000 (30:70)].The results showed a good release of tinidazole from PEG bases compared to lipophilic bases because of the interaction between the drug and triglycerides of the lipophilic bases. Also the non ionic surfactants increase the release of tinidazole from witepsole H-15 base containing suppository and the increase was greater for span 80 than tween 80.Also the influence of temperature and storage period on the physical properties and release was investigated by storing the prepared suppositories at 4˚C and 25˚C for 1, 15, 30 and 45 days. The results appeared that the temperature of storage affect the release of tinidazole from witepsole H-15, but had no effect on physical properties of the suppositories. While the storage period at both temperatures had some effects on the physical properties. On the other hand, temperature of storage affects the physical properties of polyethylene glycol suppositories and release of the drug, in contrast to the period of storage, which had no effect.The expiration date of tinidazole in formula containing polyethylene glycol 4000:1000 (30:70) was found to be about 3.3 years.

Self-Microemulsifiyng Suppository Formulation of β-Artemether

Parasitic diseases are of immense global significance as around 30% of world's population experiences parasitic infections. Among these, malaria is the most life-threatening disease. Various routes of administration have been explored for delivering antimalarial actives. The present investigation aims at formulating self-microemulsifying suppositories of β-artemether with faster onset of action and prolonged effect to be administered by rectal route. These were compared with conventional polyethylene glycol suppositories with respect to melting range, rheology, texture analysis, disintegration time, self microemulsification time, particle size, and drug content. In vitro drug release was studied by using USP apparatus II. Further, the suppositories were evaluated in murine model against virulent rodent malaria parasite Plasmodium berghei wherein the developed self-microemulsifying suppositories could sustain the activity (94%) for 20 days post infection. The survival of animals was also better as compared to the conventional formulation.

Preparation and in vitro evaluation of suppositories of halofantrine hydrochloride

Halofantrine (HF) hydrochloride is commercially available only as oral dosage forms. Limitations of oral dosing of the drug coupled with non-availability of the safe parenteral preparations prompted the need to develop and evaluate suppository HF formulations, which may serve as a practical alternative. The effects of type of suppository base and incorporation of non ionic surfactants on in vitro release characteristics of HF from suppositories were investigated. The release rates were determined using a modification of the continuous flow bead-bed dissolution apparatus for suppositories. The results showed that the drug release from water-soluble base (polyethylene glycol) was significantly greater than that from lipophilic bases (Shea butter and Witepsol H15) (P surfactants (Tweens 20 and 80, Spans 20 and 60) at different concentrations did not improve the in vitro availability of the drug from composite polyethylene glycol base (1500:4000, 80:20, w/w) suppositories. The extent of drug release was very low (maximum of 2.3%) It is suggested that further studies are required for development of modalities to enhance the release of halofantrine from polyethylene glycol suppositories so as to optimize this dosage formulation of the drug.

Effects of absorption enhancers in chloroquine suppository formulations: I: In vitro release characteristics

The need to develop chloroquine suppository formulations that yield optimal bioavailability of the drug has been emphasized. This study demonstrates the effects of incorporation of known absorption-enhancing agents (nonionic surfactants and sodium salicylate) on the in vitro release characteristics of chloroquine from polyethylene glycol (1000:4000, 75:25%, w/w) suppositories. The release rates were determined using a modification of the continuous flow bead-bed dissolution apparatus for suppositories. Results showed that the extent of drug release from suppositories containing any of three surfactants (Tween 20, Tween 80 and Brij 35) was 100%, whereas 88% release was obtained with control formulation (without enhancer) ( P<0.05). However, Tween 20 was more effective than Brij 35 and Tween 80 in improving the drug release rate. There was a concentration-dependent effect with Tween 20, and 4% (w/w) of this surfactant was associated with the highest increase in the rate of drug release from the suppositories. Sodium salicylate at a concentration of 25% (w/w) also significantly enhanced the drug release rate, but a higher concentration of the adjuvant markedly reduced both the rate and extent of drug release. Combined incorporation of Tween 20 and sodium salicylate did not significantly modify ( P>0.05) the rate of drug release when compared to the effect of the more effective single agent. Due to their effects in improving the drug release profiles coupled with their intrinsic absorption-promoting properties, it is suggested that incorporation of 4% (w/w) Tween 20 and/or 25% (w/w) sodium salicylate in the composite polyethylene glycol chloroquine suppository formulations, may result in enhancement of rectal absorption of the drug. This necessitates an in vivo validation.

Formulation, in-vitro release and ex-vivo spasmolytic effects of mebeverine hydrochloride suppositories containing polycarbophil or polysorbate 80

The release of mebeverine hydrochloride, in two different strengths 100 and 200 mg, from different suppository bases was studied in-vitro to choose the best base to be used in-vivo. The results showed that the fastest release of the drug was from polyethylene glycol 4000 suppository base. On studying the effects of the suppositories on some spasmogens on the isolated guinea-pig ileum the polyethylene glycol suppository containing 100 mg drug gave zero antagonism to acetyl choline (ACh), histamine and barium chloride (BaC1 2). Addition of 1% Tween 80 or 5% polycarbophil to the suppository formulation resulted in 33.3, 29.5, 12.1 and 25.3, 32.7 and 25.7% antagonism to ACh, histamine and BaC1 2, respectively. The suppository formulation containing 200 mg drug produced 60, 33.3 and 60% antagonism to the three agonists arranged in the same order previously mentioned. The addition of 1% Tween 80 or 5% polycarbophil to the formulation resulted in a significant increase in the drug antagonism to the three agonists producing 86, 65, 62 and 90, 66 and 90% antagonism, respectively. Weighing the suppository remaining after 2 h of administration revealed that addition of 1% Tween 80 to the formulation increased significantly ( P < 0.05) the dissolution of the suppository by 52–58% indicating the wetting effect of that additive. While, addition of 5% polycarbophil although improved the availability of the drug it did not affect the dissolution of the suppository indicating the adhesive effect that the polycarbophil exerts between the particles.

Effect of polycarbophil concentration on diclofenac sodium bioavailability from suppositories in beagle dogs

The effect of polycarbophil in different concentrations (0, 5, 10 and 20% w/w) on the bioavailability of diclofenac sodium from polyethylene glycol suppositories was studied in six beagle dogs. The in-vivo data showed that the 5% concentration of polycarbophil is the best concentration to be used in formulating polyethylene glycol suppositories containing diclofenac sodium. At this concentration, the suppositories showed a relative bioavailability of 115.17% compared to that of suppositories containing 0% polycarbophil. The other two concentrations of polycarbophil (10 and 20%) gave relative bioavailability of 56.46 and 50.21%, respectively. The 5% polycarbophil concentration resulted in the highest C max (6.35 ± 1.06 μg/ml) compared to 5.54 ± 1.21, 1.98 ± 0.70 and 1.93 ± 1.06 μg/ml for suppositories containing 0, 10 and 20% polycarbophil, respectively. It was also noted that as the polycarbophil concentration increased in the formulation the T max decreased indicating faster absorption. Also, the K el values decreased and the t 1 2 values increased indicating slower release of the drug from the formulation as the polycarbophil concentration increased. Polycarbophil as a bioadhesive is capable of inducing faster absorption and its effect on plasma concentration and bioavailability is dependent on its percentage used in the formulation.

Rectal absorption of omeprazole from suppositories in rabbits

Rectal absorption of omeprazole, a proton pump inhibitor, from suppositories was studied in rabbits. The suppositories were prepared by the conventional melting method with two types of bases, water-soluble polyethylene glycol (PEG) 4000 and oil-soluble Witepsol H15 bases, and administered intrarectally (ir) to rabbits at a dose of 10 mg omeprazole/kg. The plasma omeprazole concentration-time profiles of the two suppositories were compared with those following intravenous (iv) administration of the same dose. There were no significant differences between the two suppositories in bioavailabilities and peak plasma concentrations (Cmax). Bioavailabilities and Cmax of PEG- and Witepsol suppositories were 30.3 and 33.9%, and 7.0 and 5.6 μg/ml, respectively. However, PEG suppository showed significantly (P<0.05) shorter time to reach peak plasma concentration (Tmax), mean absorption time (MAT) and mean residence time in the plasma (MRT) than Witepsol suppository. The Tmax MRT and MAT were 25.0, 83.0 and 38.5 min for PEG suppository, but were 90.0, 122.5 and 78.0 min for Witepsol suppository, respectively. These differences between the two suppositories could be explained by the difference in the in vitro dissolution rates between the suppositories. The dissolution of omeprazole from PEG suppository was reportedly much faster than that from Witepsol suppository. It suggests that plasma profiles of omeprazole, especially Cmax, MAT and MRT, could be controlled by modifying thein vitro dissolution rate of the drug from the suppositories. Above results suggest that rectal suppository is worth developing as an alternative dosage form of omeprazole to the conventional oral preparations which need sophisticated treatments, such as enteric coating, to prevent acid degradation of the drug in the stomach fluid.

Effect of polycarbophil concentration on in vitro release and in vivo availability in beagle dogs of dihydroergotamine mesylate suppositories

The effect of different concentrations (5, 10 and 20% w/w) of polycarbophil on the in vitro release and in vivo availability of dihydroergotamine mesylate from polyethylene glycol suppositories was studied. In vitro release data showed that as the polycarbophil concentration in the suppositories increased, the release rate decreased. The in vivo data revealed that suppositories containing 5% polycarbophil resulted in a significant ( p < 0.05) reduction in C max and non-significant decrease in AUC and produced 62% relative bioavailability compared to that of polyethylene glycol suppositories containing 0% polycarbophil (control). The addition of 10% polycarbophil to the suppository formulation resulted in a lower reduction in C max and AUC than the addition of 5% and gave 78.9% relative bioavailability. The suppositories containing 20% polycarbophil produced higher C max, AUC, and relative bioavailability (127%) compared to the control. The concentration of polycarbophil in dihydroergotamine suppository formulations is critical in determining the release rate of the drug and its bioavailability.

Bioavailability of sustained release indomethacin suppositories containing polycarbophil

The bioavailability of indomethacin from polyethylene glycol base, commercial suppositories Indocid ∗, MSD and from polyethylene glycol base containing 5, 6 and 8% of polycarbophil, with the purpose of obtaining a controlled release suppositories, was determined in dogs. The results show that polycarbophil as a bioadhesive increased absorption and improved the bioavailability of indomethacin where the areas under the curves for the commercial suppositories and those containing 0, 5, 6 and 8% polycarbophil were 19.5, 14.9, 31.2, 21.4 and 21.2 μ h ml −1, respectively. The maximum plasma concentration ( C max) and the time to reach C max ( t max) were 4.76, 2.98, 4.50, 2.36 and 1.29 μg/ml and 1, 1, 1, 1 and 12 h for the commercial suppositories and those containing 0, 5, 6 and 8% polycarbophil, respectively. The data indicate that as the polycarbophil concentration increased from 0 to 5% in the polyethylene glycol suppositories, the plasma levels and bioavailability improved significantly ( p < 0.1, Student's t-test), whereas on increasing from 5 to 6 and 8% the plasma levels and bioavailability decreased significantly ( p < 0.05). At 8% polycarbophil concentration, sustained release suppositories were produced but a decrease in plasma levels was observed.

未熟児動脈管開存症治療のためのメフェナム酸坐剤の開発と評価：基剤による放出制御と健常人における体内動態

Two types of mefenamic acid (MA) suppositories were prepared, one with Vosco®, an oleaginous base (Vosco suppository) and another with polyethylene glycol (PEG), a watersoluble base (PEG suppository). The crystallinities of MA in the Vosco and PEG suppositories, the in vitro release behaviors of MA from them, and the pharmacokinetics of MA following their rectal administarations to healthy volunteers were respectively compared. X-ray diffractometry revealed that MA in the Vosco suppository was mainly dispersed in a crystal form, whereas MA in the PEG suppository was disseminated in the amorphous state, with the in vitro release of MA from the PEG suppository being faster. MA in the Vosco or PEG suppository was chemically stable, and the in vitro release behavior of MA from each suppository did not change after storage for 2 months at 5°C. The serum MA maximum concentration (Cmax) and the time to reach Cmax after rectal administration of the PEG suppository appeared to be respectively higher and to be shorter than those of the Vosco suppository. The areas under the serum MA concentration-time curves (AUCs) from zero time to 8 h for the Vosco and PEG suppositories were 3.2 and 4.1 μg·h/ml, respectively, and their values were not significantly different. It was concluded that the PEG suppository presented a faster release characteristic of MA than did the Vosco suppository and that the serum MA concentration profiles arising after administration of these suppositories reflected their release characteristics.

Differential Thermal Analysis of Polyethylene Glycol and Glycerol Monostearate Suppository Bases Containing Theophylline

AbstractWater soluble polyethylene glycol 4000 (PEG4) suppositories were prepared containing 4% (w/w) theophylline. Various concentrations of polyethylene glycol 1000 (PEG1) and glycerol monostearate (GMS) were also added. Differential thermal analysis (DTA) of the PEG4 and PEG1 combination suppositories showed no melting endotherm for theophylline. But when theophylline concentration in the base was 12% (w/w) and above, sharp endothermic peak of theophylline was obtained. In contrast, when GMS was added as a base material above 50% (w/w) with PEG4, the melting endotherm of theophylline (4%, w/w) appeared at 273-274°C. The melting endotherm of the suppository bases increased up to 2 to 4°C due to storage at 4°C for six months.

Suppository formulation of amodiaquine - In vitro release characteristics

AbstractIn vitro release characteristics of amodiaquine hydrochloride from suppositories were studied. Results showed that water soluble bases (polyethylene glycol and glycero-gelatin) and water miscible synthetic fatty base (Witepsol W45) are superior to natural fatty bases (theobroma oil and shea butter) in terms of their ability to release amodiaquine hydrochloride.The in vitro availability of amodiaquine from polyethylene glycol suppository (the suppository which gave the highest rate and extent of release) was compared with its in vitro availability from tablets (CamoquinR) under the same experimental conditions. Polyethylene glycol suppository was found to be superior to the tablet.

Rectal Absorption of Phenytoin in Rabbits from Polyethylene Glycol Suppositories

AbstractVarious suppositories containing phenytoin and phenytoin sodium were formulated with different polyethylene glycol combinations. The three formulae that had the best in vitro release rate were administered to rabbits. Phenytoin was well absorbed from the suppositories, and the results show that rectal administration of phenytoin can be an alternative to oral administration.