Suppository Dosage Form Research Articles

Formulation and evaluation of bioadhesive suppository dosage form

The current study aims to formulate and evaluate a dosage form for bio-adhesive suppositories. Using CB and HPKS (CE and SS) as suppository bases, optimized manufacturing techniques successfully made suppositories containing bio-adhesive polymers (CBP, PVP, HPMC, and CMCTS). Analyzing dosage forms is crucial to determining the quality of a product. The suppositories produced in this investigation had good weight consistency, with minimal variation (±1%) between the goal and actual weight. All formulations showed melting values between 32.5 and 35.5 degrees Celsius, while the melting points of suppositories made with CE and SS were 1-2 degrees Celsius greater than those of CB suppositories. Incorporating bio-adhesive polymers did not cause a substantial change in the suppositories' melting point (less than ± 1 °C), keeping it around body temperature and appropriate for rectal administration. More than 95% of the required DcNa content was present in every formulation tested. All formulations, however, had softening durations of three to seven minutes, which was suitable for rectal medication delivery. The physical characteristics of the suppositories this chapter looked at were determined to be appropriate for administration by the rectal route. Compared to CB suppositories, HPKS suppositories have an additional benefit due to their longer softening time and melting point of 34.5 ± 1 °C.

An assessment of parents\u2019 knowledge and awareness regarding paracetamol use in\xa0children: a\xa0cross-sectional study from Palestine

BackgroundParacetamol, also known as acetaminophen, is one of the most common antipyretic and analgesic over-the-counter (OTC) medicines administered to children due to its efficacy, safety, and availability in many pharmaceutical forms, including suppositories, syrup, and drops. Parents frequently administer the wrong dose of paracetamol by mistake for their children, as reported by many previous studies. We aimed in this study to assess parents’ knowledge, attitudes, and practice regarding paracetamol dosing and toxicity, as well as their awareness regarding paracetamol-containing products.MethodsThis was a cross-sectional study that targeted parents of children seeking healthcare services at primary health care centers in the Nablus area in the West Bank, Palestine. We used questionnaire-based interviews with parents for data collection.ResultsA total of 300 parents were included in the study. Most of the caregivers surveyed were (87%) females (mothers). About half the parents (50.9%) reported previously using paracetamol as an antipyretic in children under the age of six. A quarter (25.4%) preferred the syrup forms, while 33.8% preferred the suppository dosage form. Medical personnel was the primary source of information for half the caregivers (51.2%). The mean knowledge score about paracetamol was 2.1 (SD = 1.4) out of 6, and the median was 2.0 with an interquartile range of 1.0–3.0. Two hundred seventy-four (95.5%) of the participants scored less than 80% and were considered to have insufficient knowledge. Only 50.9% of parents recognized that paracetamol overdose could result in serious harm.ConclusionsWe found a serious lack of knowledge regarding paracetamol dosing, administration, and potential toxicity among Palestinian parents. We recommend raising awareness regarding this problem among healthcare providers and authorities and working on plans that aim to provide caregivers with accurate and adequate information on dosing, formulation, side effects, and other aspects of paracetamol use, as well as developing effective educational plans targeting healthcare providers, as well as the public.

Development of the composition and pharmacokinetic studies of suppositories with combined substance of bacteriophages

The aim of this study was to develop a suppository dosage form based on the bacteriophages cocktail. To achieve this, using patented technology, highly active sterile phage lysates were obtained, auxiliary components were selected and the finished dosage form was designed - suppositories with the initial high specific antibacterial activity that persists after absorption through the intestinal mucosa, which was confirmed during pharmacokinetic studies in experimental animals.During the development of suppositories based on bacteriophages cocktail microbiological, molecular genetics, biotechnological methods and preclinical studies were used.

Formulation, in vitro and Bioavailability Assessments of Ranitidine Rectal Suppositories

The objective of the current work was to develop and evaluate suppository dosage form in order to improve ranitidine bioavailability as a substitute to the oral administration. Suppocire (different grades), Witepsol W25 and polyethylene glycol (PEG) were used as suppository bases and prepared by molding method. The prepared formulations were examined for hardness, disintegration time, melting point, content uniformity, drug release, stability and bioavailability. The hardness ranged from 3.82 to 12.53 kg and disintegration time from 13.32 to 28.22 min. The melting points of fatty bases had values from 33.94 to 36.82±0.36ºC while PEG based suppositories melting points were directly proportional chain length. Higher content uniformity was observed in PEG based suppositories due to easy incorporation of RT into water soluble base. Release was affected by hydroxyl value and molecular weight (in cases of fatty and PEG bases respectively). All formulations were relatively stable after 12 months. In vivo studies of all formulations exhibited double peak phenomena. PEG based formula (S8) showed significant higher Cmax (10.05±1 μg/ml) and AUC0-12 (58.313±3.9 µg.h/mL) than fatty bases and oral solution. In conclusion, rectal administration of S8 could be prepared as an alternative to the oral dosage form to improve bioavailability and overcome the first-pass metabolism.

Pharmacokinetics and Tolerability of Δ9-THC-Hemisuccinate in a Suppository Formulation as an Alternative to Capsules for the Systemic Delivery of Δ9-THC

The objectives of this study were: (1) to assess the safety, tolerability, and pharmacokinetics of ascending doses of Δ⁹-tetrahydrocannabinol-hemisuccinate (THC-HS) after rectal administration as suppositories in male volunteers; and (2) to compare the pharmacokinetics of oral administration of Δ⁹-tetrahydrocannabinol (Δ⁹-THC) with an equivalent amount of Δ⁹-THC delivered as THC-HS via the suppository formulation. In support of the pharmacokinetic evaluations, an analytical method was developed and validated for the determination of Δ⁹-THC and for its major circulating metabolites 11-hydroxy-Δ⁹-tetrahydrocannabinol (11-OH-THC) and 11-nor-Δ⁹-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) in human plasma. Δ⁹-THC, 11-OH-THC, and THC-COOH were extracted from plasma using solid phase extraction and analyzed by liquid chromatography-tandem mass spectrometry. The limits of detection and quantitation for all 3 analytes were 0.25 and 0.5 ng/mL, respectively. The method was validated over the range of 0.5–25 ng/mL. This method was used to quantify Δ⁹-THC and any THC-HS as Δ⁹-THC due to the inclusion of a hydrolysis step as part of the extraction procedure. Therefore, Δ⁹-THC measured was the total THC (free Δ⁹-THC plus Δ⁹-THC derived from THC-HS). The assay was reproducible for the measurement of all 3 analytes, with a variability of 7.2, 13.7, and 8.3%, respectively, at the 1 ng/mL level. The method was then used to assess the pharmacokinetics of Δ⁹-THC and metabolites from the suppository dosage form in doses equivalent to 1.25, 2.5, 5, 10, and 20 mg Δ⁹-THC per suppository as THC-HS. Systemic exposure to Δ⁹-THC, administered as THC-HS suppository, increased broadly dose proportionally. Systemic exposure and C_{max (obs)} estimates for 11-OH-THC and THC-COOH generally increased subproportionally. The pharmacokinetic profiles of Δ⁹-THC and metabolites were also compared after oral administration of 10 mg Δ⁹-THC (as dronabinol capsules) and after administration of 10 mg equivalents of Δ⁹-THC as THC-HS in suppository form. Total systemic exposure to Δ⁹-THC was considerably higher following rectal administration of THC-HS than after oral administration. The Δ⁹-THC area under the plasma concentration versus time curve (AUC_(0–_∞₎) for THC-HS was 2.44-fold higher (90% confidence interval: 1.78, 3.35) than for the capsule administration.

Some physical properties of novel Cannabis suppositories formulated with theobroma oil

As part of development efforts for a suitable dosage form, crude Cannabis resin was formulated into suppository dosage form using theobroma oil and the physical properties of the suppositories were evaluated. The following physical properties were evaluated: appearance (texture, presence or absence of entrapped air, contraction holes), liquefaction time, uniformity of weight and in-vitro release profile of the crude marijuana resin from the suppositories. The torpedo shaped suppositories were smooth in texture with absence of entrapped air and contraction holes. The suppositories had uniform greenish brown colour and low weight variation. The liquefaction time was also low. The 300 mg Cannabis crude in 4 % Tween 85 showed highest melting time (11.67 ± 057 min) while the incorporation of Tween 85 improved the release profile (0.0452-0.0650 %) in different batches. It is possible to formulate marijuana suppositories with satisfactory physical properties; however, release profile of marijuana from the suppository bases was generally low even though the addition of Tween 85 greatly enhanced drug release. Key words: Crude Cannabis resin, sustained release, liquefaction time, weight uniformity, release profile.

Separation and determination of impurities in paracetamol, codeine and pitophenone in the presence of fenpiverinium in combined suppository dosage form

A new HPLC method for separation and determination of impurities in paracetamol, codeine phosphate hemihydrate and pitophenone hydrochloride in the presence of fenpiverinium bromide in combined suppository dosage form was developed and validated. The separation of paracetamol and its impurities 4-aminophenol, 4-nitrophenol, 4-chloracetanilid; codeine and its impurities methylcodeine, morphine, codeine dimer and 10-hydroxycodeine; pitophenone and its impurities 2-[4-[2-(1-piperidinyl)ethoxy]benzoyl] benzoic acid, 2-[4-[2-(1-piperidinyl)ethoxy]benzoyl]benzoic acid 2-(1-piperidinyl)-ethyl ester, methyl ester of 2-(4-hydroxybenzoyl) benzoic acid and fenpiverinium was achieved by using ion-pair reversed phase liquid chromatography with UV detection. Validation parameters such as the precision, accuracy, linearity, limit of detection (LOD), limit of quantification (LOQ) and robustness were verified for all the mentioned impurities of codeine phosphate hemihydrate and 4-aminophenol and 2-[4-[2-(1-piperidinyl)ethoxy]benzoyl] benzoic acid as the main degradation products of paracetamol and pitophenone hydrochloride, respectively. The described method was found to be useful for analysis of the stability samples and therefore suitable for routine purity testing of the drug product.

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.

Nondestructive prediction of the drug content of an aspirin suppository by near-infrared spectroscopy

Background: A suppository dosage form has a rapid effect on therapeutics, because it dissolves in the rectum, is absorbed in the bloodstream, and passes the hepatic metabolism. However, the dosage form is unstable, because a suppository is made in a semisolid form, and so it is not easy to mix the bulk drug powder in the base. Aim: This article describes a nondestructive method of determining the drug content of suppositories using near-infrared spectrometry (NIR) combined with chemometrics. Method: Suppositories (aspirin content: 1.8, 2.7, 4.5, 7.3, and 9.1%, w/w) were produced by mixing an aspirin bulk powder with hard fat at 50 °C and pouring the melt mixture into a plastic mold (2.25 mL). NIR spectra of 12 calibration and 12 validation sample sets were recorded 5 times. A total of 60 spectral data were used as a calibration set to establish a calibration model to predict drug content with a partial least-squares (PLS) regression analysis. NIR data of the suppository samples were divided into two wave number ranges, 4000–12500 cm−1 (LR), and 5900–6300 cm−1 (SR). Calibration models for the aspirin content of the suppositories were calculated based on LR and SR ranges of second-derivative NIR spectra using PLS. Results: The models for LR and SR consisted of five and one principal components (PC), respectively. The plots of predicted values against actual values gave a straight line with regression coefficient constants of 0.9531 and 0.9749, respectively. The mean bias and mean accuracy of the calibration models were calculated based on the SR of variation data sets, and were lower than those of LR, respectively. Conclusion: Limiting the wave number of spectral data sets is useful to help understand the calibration model because of noise cancellation and to measure objective functions.

The efficacy of urine data in comparative bioavailability of proguanil after oral and rectal administration in man

The bioavailability of proguanil formulated as suppository, was compared to the tablet formulation in a bid to evaluate the utility of the suppository dosage form as means of administering proguanil in children and high-risk groups, such as sickle cell patients, who may not tolerate oral route of administration. The study was a completely randomized cross over involving administration of 200 mg of proguanil suppository and tablet to twelve healthy volunteers. Biological fluids such as urine and blood were collected before and at predetermined time intervals following administration of the drug. The biological samples were analyzed for the unchanged proguanil using an earlier reported method. The relative bioavailability of proguanil suppository as compared to the tablet dosage form was found to be about 61% from both urine and plasma data. The findings showed for the first time that proguanil suppository could be sufficiently bioavailable and may therefore be useful in chemoprophylaxis of malaria in sickle cell patients and children, particularly under such conditions that made oral route become impracticable. Key words: Proguanil, tablets, suppositories, plasma and urine data, bioavailability.

Salbutamol Sulfate Suppositories: Influence of Formulation on Physical Parameters and Stability

Purpose. To prepare and evaluate a suppository dosage form of salbutamol sulfate. The prepared formulae with and without different concentrations of gels were tested for hardness, melting time, content uniformity, and drug release. The stability of some of the selected formulae was assessed. Methods. Salbutamol sulfate was formulated as a rectal suppository with emulsifying fatty bases (suppocire and witepsol) and water-soluble bases (PEG) adopting the molding from a melt technique. Physical characteristics and dissolution profiles of the prepared formulations were determined as the responses. The effects of adding gels, methyl cellulose (MC), and Eudispert (Eud) and their concentrations (1, 3, and 6%) on these responses were also investigated. Formulations showing high rank order were scaled up for shelf-life stability study for one year. Results. The results showed that all the investigated formulae have acceptable physical characteristics with respect to hardness, melting time (except F7), and uniformity of drug content. The amount of drug dissolved in 100 min of dissolution time was inversely affected by the melting point of the fatty base. The release from PEG bases was found to be molecular weight dependent. Addition of 1% MC or Eud gel increased the release from all the investigated formulae. Increasing gel concentration to 3% then to 6% showed different effects on the release. The degradation of salbutamol sulfate in the investigated formulae was found to be a first-order reaction. Conclusions. Rectal suppository of salbutamol sulfate could be prepared as an alternative to the oral dosage form to circumvent the first-pass metabolism.

Investigation of Ethacrynic Acid and Random-methyl- β -cyclodextrin Binary Complexes

Cyclodextrin complexation was applied to achieve better aqueous solubility of the drug and to formulate suppositories. Binary products were prepared in several mole ratios by two different methods. The dissolution profiles and in vitro membrane diffusion behaviour of the compositions were investigated. Thermoanalytical studies were performed in order to confirm inclusion complex formation. Compositions were selected for further detailed investigations and for incorporation into suppository dosage form.

Solutol and Cremophor Products as New Additives in Suppository Formulation

ABSTRACTOur research has a double purpose. On the one hand, doctors have expressed the need to formulate a rectal suppository dosage form from diuretic ethacrynic acid, which would add to the choice of treatment methods and thereby increase the possibilities of individual cure. On the other hand, the liberation and thereby the bioavailability of poorly-soluble ethacrynic acid needs to be enhanced, and for this purpose solubility-increasing additives new to rectal therapy were used. Solutol HS 15, Cremophor RH 40, and Cremophor RH 60 were used as additives in concentrations of 1, 3, 5, and 10%. The quantity of drug released changed as a function of additive concentration. Depending on the acceptor phase, the best results were achieved with an additive concentration of 1–3%, which is related to the optimal additive quantity accumulated on the boundary surface.

Study on the release of indomethacin from suppositories: in vitro-in vivo correlation

The in vitro dissolution kinetics of three different suppository formulations of indomethacin was studied using two different apparatuses, namely, a flow-through cell (Dissotest ®) and a dialysis rotating cell (Pharmatest ®). A comparison between both apparatuses was carried out and two types of dissolutions became apparent depending on whether the excipient used in the formulation was either hydrophilic or lipophilic. The distinction between dissolution profiles was more evident using the flow-through cell. From the in vivo curves parameters furnished by the manufacturers, in vitro/in vivo correlations were performed. A linear relationship was established between the in vitro results obtained and the in vivo percentages absorbed that were calculated according to the Wagner-Nelson method. Simulated blood concentration-time curves were generated from the in vitro released data and the pharmacokinetic parameters obtained. A good superimposition of the experimental plasma concentrations and the simulated curves was obtained with the flow-through cell and the hydrophilic suppository dosage form whereas the simulation with the lipophilic suppository gave imperfect results irrespective of the apparatus used.

Pharmacokinetics of a 5‐aminosalicylic acid enteric‐coated tablet and suppository dosage form

An Eudragit-L coated oral 5-aminosalicylic acid (5-ASA; mesalazine) product (Mesasal), has been formulated to deliver 5-ASA to the distal small intestine and colon for the treatment of inflammatory bowel disease. The purpose of this study was to compare the pharmacokinetic profile of this product to sulphasalazine (SASP; Salazopyrin) and to assess the pharmacokinetics of a suppository 5-ASA dosage form. Twelve healthy volunteers randomly received four single doses of 5-ASA delivering formulations not less than 1 week apart. (a) Mesasal tablets, 2 x 250 mg, fasting; (b) Mesasal tablets, 2 x 250 mg, fed; (c) Salazopyrin tablets, 3 x 500 mg (corresponding to 576 mg 5-ASA), fasting; and (d) Mesasal suppository, 1 x 500 mg, fasting. Plasma 5-ASA and acetyl-5-ASA (Ac-5-ASA) concentrations were followed for 48 h and urine and faecal concentrations for 72 h. Mesasal tablets (fasting) produced a greater area under the concentration-time curve (AUC), peak and time to peak for both plasma 5-ASA and Ac-5-ASA than Salazopyrin. Median urinary recovery values were 21.7% for Salazopyrin and 35.5% for Mesasal (fasting) (P less than 0.01). This means that the systemic absorption was higher after Mesasal than after Salazopyrin. The total faecal recovery values were 38.3 and 26.5%, respectively (NS). Except for a delay of 1.5-.3 h in the time to peak of 5-ASA and Ac-5-ASA plasma levels, the pharmacokinetics of Mesasal tablets were essentially the same in fasting or fed subjects. Suppository administration of 5-ASA resulted in a low median urinary recovery of 10.8%.

Biopharmaceutics of rectal administration of drugs in man IX. Comparative biopharmaceutics of diazepam after single rectal, oral, intramuscular and intravenous administration in man

Rectal absorption of diazepam was studied in man and compared with intravenous, intramuscular and oral administration. Plasma concentrations of diazeparn were measured by means of HPLC analysis after a single dose of 10 mg diazeparn in a cross-over study in 9 healthy volunteers. Plasma concentration—time curves following intravenous administration were described by a tri-exponential function consistent with a three-compartment model system. It was calculated that the drug will not exhibit measurable first pass metabolism. Comparing the absorption rate constants it appeared that rectal absorption of a solution of diazeparn proceeded significantly ( I <0.05) more rapidly than absorption after oral and intramuscular administration. Absorption from a macrogol suppository dosage form was rather slow. The mechanism of the rapid rectal absorption of diazeparn from the solute state was discussed. No essential difference in bioavailability was observed between the intramuscular injection, rectal solution and tablets as compared with the intravenous injection. Only for the suppository dosage form was bioavailability calculated to be significantly lower.

Biopharmaceutics of rectal administration of drugs in man 7. Absorption rate and bioavailability of phenobarbital and its sodium salt from rectal dosage forms

In this report it will be shown that rectal administration of phenobarbital and its sodium salt can be looked upon as an alternative route of administration. Plasma phenobarbital concentrations were measured in 6 volunteers after a single oral dose (219 mg) of sodium phenobarbital and after single rectal doses of phenobarbital (200 mg) or sodium phenobarbital (219 mg). In the case of the rectally administered aqueous dosage forms of phenobarbital no distinct difference in absorption rate occurred whether the sodium salt or the free acid was used. Rectal administration of both types of micro-enemas results in absorption which is less rapid than after oral administration of the sodium salt. However, the final and total absorption of phenobarbital and its sodium salt after 6.5 h is practically complete, compared with oral administration. The in vitro release of phenobarbital from fatty suppositories using a coarse powder (125–250 μm) of sodium phenobarbital and with a fine powder (<20 μm) of phenobarbital showed marked differences. The rectal absorption profile of the aqueous and fatty dosage forms of sodium phenobarbital in vivo was quite similar. A much slower absorption rate was observed if the free acid was used in the fatty suppository dosage form.

Drug Absorption from the Rectum I: Suppository Bases: A Preliminary Report

Studies were begun to determine the process(es) by which drugs may be absorbed from the rectum, and the effect of suppository dosage form on these process(es). Using dogs, whose anatomy closely resembles that of humans, plasma salicylate levels from salicylic acid and sodium salicylate incorporated into four different suppository bases were studied. It was found that the drugs were released and absorbed equally well from cocoa butter, while from a base composed of a mixture of synthetic glycerides, a polyethylene glycol base, and from polyoxyethylene (4) sorbitan monostearate, salicylic acid gave higher plasma salicylate levels. A passive diffusion process is proposed. In the studies to follow, the effect of suppository base and physicochemical characteristics of the drugs on absorption from the rectum will be explored in detail.