Suppository Preparation Research Articles

PHARMACEUTICAL ANALYTICAL STUDY OF VIMALA VARTI: AN AYURVEDIC OPHTHALMIC PREPARATION

Varti Kalpana, a derivative of Vati Kalpana, represents Ayurvedic suppository preparations with specific therapeutic applications. Vimala Varti, an herbal ophthalmic suppository detailed in the Sahasra Yogam under Netraroga Chikitsa, addresses various eye ailments such as Timira, Kacha, Netra Kandu, and Patala Roga. This formulation comprises eight herbal ingredients and one Bhavana Dravya. The preparation of Vimala Varti involved the Bhavana method. A comprehensive pharmaceutical study was conducted to evaluate the organoleptic and phytochemical parameters of Vimala Varti, ensuring its suitability for ophthalmic use. The final product was assessed for various parameters, including pH, hardness, friability, and loss on drying etc. pH was 6.26, hardness-5, friability 0.7.89%, loss on drying 13.6%, uniformity of weight was within the limit, total ash -3%, water soluble extractive 19.2%, acid insoluble ash 1%. These parameters can be considered the preliminary standards for Vimala Varti. This study highlights the potential of Vimala Varti as a reliable Ayurvedic treatment for eye disorders, warranting further clinical research to validate its efficacy and therapeutic benefits.

Rectal thionamide administration in the setting of thyroid storm: a case report and review of the literature.

Thyroid storm is a clinical diagnosis characterized by life-threatening multisystemic organ involvement in the setting of uncontrolled hyperthyroidism. Current estimates suggest a mortality rate of up to 30%. Treatment often consists of the administration of thionamide medications, iodine solution(s), corticosteroids, and beta-blockers; in extreme circumstances, both plasmapheresis and thyroidectomy are subsequent therapeutic options. Thionamides are typically administered orally, with the intent of preventing further thyroid hormone synthesis; however, in the literature, there are instances whereby oral access cannot be obtained, and alternative routes of administration are required. We present a case of a patient who presented with a thyroid storm due to lack of adherence to methimazole. During admission, he was found to have significant abdominal pain and ultimately a duodenal perforation requiring strict nil-per-os (NPO) status, due to which he was unable to receive oral thionamides. Due to the lack of availability of intravenous formulations of thionamides in the United States, this patient was treated with an enema compound of propylthiouracil for a total of five per rectum (PR) doses. He would later develop hepatocellular injury, requiring discontinuation and eventual transition to oral methimazole. The literature pertaining to alternative-route thionamide administration is scant, and therefore this case report and literature review is written to provide an up-to-date review and further educate all levels of clinicians about this infrequent (but emergent) situation. Thyroid storm is a clinical diagnosis for which urgent recognition is required to prevent untoward mortality. Treatment for thyroid storm requires prompt administration of thionamides, iodine, corticosteroids, and beta-blockers. In extreme circumstances, treatment considerations include plasmapheresis and thyroidectomy. Infrequently, patients with a thyroid storm may not be able to tolerate oral medications, for which alternative routes of access are required. Currently, available alternatives include intravenous methimazole (in Europe and Japan), as well as both enema and suppository preparations of propylthiouracil and methimazole.

Role of Sertaconazole in the Treatment of Dermatophytosis

Dermatophytosis is a major health burden worldwide and is now increasing day by day. Dermatophytosis is also becoming increasingly unresponsive to topical conventional antifungals now a day. Newer topical antifungals may be more effective in these patients. Sertaconazole is a new, broad spectrum, fungicidal and fungistatic imidazole with added antipruritic and anti-inflammatory activity that may be effective and beneficial in improving the quality of life for the patient with dermatophytoses. It is indicated in the European Union(EU) for the treatment of superficial skin mycoses such as dermatophytosis (including tinea corporis, tinea cruris, tinea manus, tinea barbae and tinea pedis), cutaneous candidiasis, pityriasis versicolor and seborrhoeic dermatitis of the scalp, and in the US for tinea pedis only. Sertaconazole has broad-spectrum antifungal activity against dermatophytes of the Trichophyton, Epidermophyton and Microsporum genera, and yeasts of the genera Candida and Cryptococcus; additionally, it is effective against opportunistic filamentous fungi and Gram-positive bacteria. Moreover, the antifungal activity of sertaconazole is maintained in clinical isolates of dermatophytes that show reduced susceptibility to other azoles. While the drug has good dermal penetration, this is not associated with systemic absorption. In clinical trials in patients with superficial mycoses, 2% sertaconazole cream applied twice daily was effective in the eradication of a range of dermatophytoses, and a significantly greater proportion of patients were cured compared with those receiving 2% miconazole cream twice-daily treatment. Both as a topical cream and suppository preparation, sertaconazole was generally well tolerated. Sertaconazole is a well-established antifungal agent, which is now available in a variety of formulations, and remains a useful treatment option particularly in patients with fungal infections resistant to other azoles. Medicine Today 2023 Vol.36 (1): 62-66

Formulation and characterisation of metyrapone suppositories for the first effective long-term use in an infant with McCune-Albright syndrome-related Cushing syndrome

ObjectivesThe aim of this project was to develop a rectal formulation of metyrapone suitable for application in an infant hospitalised with McCune-Albright syndrome (MAS)-related Cushing syndrome and to provide a...

A review on suppositories

Suppositories are pharmaceutical dosage forms that hold a crucial place in the realm of drug delivery. This review provides a comprehensive introduction to suppositories. This article explores the various aspects of suppository formulations and therapeutic applications. This review emphasizes the significance of suppositories as a valuable drug delivery option and the role they play in addressing specific patient needs. It also discusses the fundamental components of suppositories, including bases and active pharmaceutical ingredients, along with the methods of suppository preparation. The development and formulation of suppositories require a deep understanding of various factors, including base selection, drug compatibility, and patient preferences. The choice of base impacts the release and absorption characteristics of the drug, making it a pivotal consideration in suppository design. Their significance lies not only in their unique mode of administration but also in their ability to offer solutions for specific patient needs, including cases of nausea, vomiting, or difficulties with oral medication.

Process of gallnut suppository preparation

The main objective was to research the process of gallnut suppository preparation with its water extract as the main drug, and evaluate its irritation to rectal mucosa. gallnut extract was obtained by decocting method, and its suppository preparation was obtained by fusion method with semi-synthetic aliphatic esters and rose flower oil as the matrix. Weight difference and in vitro melting time limit of the suppository were assayed and UV-Vis was used to determine the contents of polyphenols, tannin and saccharide. The irritation to colon mucosa was evaluated after successive administration of 14 days to New Zealand white rabbits. Finally, the prescription compositions were determined: semi-synthetic aliphatic esters and rose flower oil with the ratio of 2:1 as the proper matrix, with the drug loading of 54%. The prepared suppository was brown, conical and smooth. The weight difference was (1.43±0.03) g, with an average melting time limit of (17±2) min. The Contents of Polyphenols, tannic and polysaccharide were 332.4, 245.0, 3.3 mg•g-1 respectively in each suppository. The results also showed that the continuous administration had no irritation to rectal mucosa. It can be concluded that the suppository was an acceptable administrate form, whose preparation process was easily controlled, and with no irritation to rectum mucosa.

Preparation and content determination of metadoxine suppository

Objective:To investigate the preparation process and to determine the content of metadoxine suppository.Methods:Suppositories were prepared with metadoxine as the main component.The content of metadoxine in the suppository was determined by HPLC method.The HPLC method was applied on a Gemini 5U-C18column(250mm×4.6mm,5μm),at35℃column temperature,with the mobile phase consisting of acetonitrile-0.1%phosphoric acid solution(1∶99),flow rate of1ml/min and the detection wavelength of 205 nm.Results:The prepared metadoxine suppository was an ecru conical solid.Metadoxine presented good linearity in the range of 20.2-101μg/ml.The standard curve equation was A=56.83 c+47.88(r=0.999 9).The recovery rates of low,medium and high concentrations(40.4,60.6,80.8μg/ml)of metadoxine were(99.97±0.032)%,(99.91±0.076)% and(99.86±0.046)%(n=3),respectively.Conclusion:The method established by this research for suppository preparation is feasible,and the content determination method could be used for the study of metadoxine suppository.

A randomised, controlled, crossover study to investigate the safety and response of 1R,2S‐methoxamine hydrochloride (NRL001) on anal function in healthy volunteers

This study aimed to assess the dose and volume effects of suppository preparations and safety of NRL001 (one of four possible stereoisomers of methoxamine hydrochloride) on anal sphincter tone using rectal suppositories in healthy adult volunteers. This was a Phase I, single-centre, randomised, double-blind, three-way crossover study during which subjects received three single doses of 1 g rectal suppositories (containing 5 or 10 mg NRL001 or matching placebo) or 2 g rectal suppositories (containing 10 or 15 mg NRL001 or matching placebo) on three separate dosing days. The outcome measures were mean anal resting pressure (MARP) variables (monitored continuously for 20-30 min before and up to 6 h after dosing), pharmacokinetics (PK) and safety assessments. Twenty-six subjects were dosed with study medication. Two subjects were withdrawn prematurely and were not included in the main analysis. There was a dose-dependent increase in anal sphincter tone (MARP) when comparing the 5 and 10 mg doses of NRL001; however, the 15 mg dose did not have a significantly greater effect than the 10 mg dose. Suppository size (1 or 2 g) did not appear to have an effect on sphincter tone. There was no evidence against dose proportionality for the PK variables, but the mean maximum plasma concentration (Cmax ) for the 1 g suppository group was higher than for the 2 g group. Twenty-one adverse events were reported in 8 (30.8%) subjects. A dose dependent decrease in heart rate was noted; however, there were no adverse events reported that were related to this reduction in heart rate. The increase in anal sphincter tone supports the potential therapeutic use of NRL001 in treating faecal incontinence, with further studies in patients required. NRL001 was well tolerated in single doses of up to 15 mg.

Improvement and Prediction of Intestinal Drug Absorption

The suppository preparation, which can improve the absorption of poorly absorbable drugs safer than commercially available suppositories, was developed by utilizing sodium laurate and taurine. Additionally, the novel oral absorption-improving system was also established by utilizing polyamines and bile acids. Furthermore, to evaluate the efficacy of these new formulations and estimate the absorbability of new drug candidates in humans, the in vitro prediction system utilizing an isolated human intestinal tissues was developed and successfully predicted the fraction of dose absorbed for several model drugs. These findings would contribute to the development of new dosage forms and new drugs for oral administration.

ON003 From motivated and compliant to empowered: Do we need an IBD nurse led self management programme?

Background: To ascertain service users level of knowledge regarding use of enema therapy and to investigate the need for the provision of a structured self management program. Methods: Patients were identified at the Inflammatory Bowel Disease (IBD) clinic in a tertiary referral centre and asked to participate in a confidential questionnaire. The purpose was twofold to assess patient knowledge and to identify barriers to compliance/adherence. Data were gathered prospectively over a 28 day study period and statistically analyzed. P values <0.05 were deemed significant. Results: Thirty-five completed questionnaires were received; 65.7% had Ulcerative Colitis; median age was 36; median time since diagnosis was 7 years; 94.2% had previously been prescribed topical therapy. There was no significant preference for use of liquid, foam or suppository preparations. The most widely used preparation was Salofalk enema (30.3%), followed by Predfoam (26.8%). 73% chose evening as the best time to take enemas (p < 0.0001). A large minority administered their topical treatment incorrectly, while standing (35%), with 43% adopting a left sided position. The majority (71.44%) stayed lying ten minutes or longer after administration rather than moving straight away or within 1 minute ( p < 0.017). Most patients (67.7%), did not change position once the enema had been administered (p = 0.0105). Compliance was good with 94% always or sometimes completed their full course of treatment as prescribed. Less than 1/3 participants took treatment for 1 week post symptom resolution, with 42% taking their prescribed course and 30% until they felt better. In addition, 70% of patients never started treatment without consulting a medical professional (p < 0.0028), indicating a potential need for greater autonomy in decision-making around treatment for IBD patients. The majority (59.5%) chose to contact the IBD nurse when having a flare. Also promisingly, when asked if interested in learning how better to manage flares independently 100% of participants agreed that this would be a desirable option. Conclusions: While acknowledging the small sample size in our study, gaps in both knowledge and confidence have been identified in this cohort. The service users have a good compliance record and a positive interaction with health professionals (mainly the IBD Nurse). Empowering patients through an IBD Nurse Led Self Management Programme would be beneficial for patients well being and would on the long term reduce the burden on the service.

Suppository Preparation: Density Factor Determination for Some Over-the-Counter Analgesic Products

Background: The formulation of analgesic suppositories by the compounding pharmacist may offer an alternative to patients who cannot take medications orally. Objective: To determine the density factor (DF) for 9 nonprescription nonsteroidal antiinflammatory drugs, aspirin, and acetaminophen for use in compounding suppositories. Methods: Nine nonprescription analgesic products were purchased from local stores in North Carolina. All products were solid dosage forms (ie, tablets, caplets, or geltabs). The solid units were pulverized with a porcelain mortar and pestle and then incorporated into a cocoa butter base for formulating the suppository. The DF estimation was evaluated according to the Paddock method. Results: The highest DF value (mean ± SD) among the products tested was for St. Joseph Aspirin (1.45 ± 0.78); the lowest value was for Motrin IB (ibuprofen) (1.06 ± 0.23). Overall, 11.1% (40/360) of all compounded suppositories had some sort of defect. The most often encountered defect was chipping (3.6%; 13/360); the least encountered was sticking to molds (0.83%; 3/360). Conclusions: A practical method for preparing compounded suppositories provides a viable alternative for patients who require analgesic medications but cannot take them orally.

Sertaconazole

Sertaconazole

PALM KERNEL OIL BLENDS AS SUPPOSITORY BASES IN THE DELIVERY OF ASPIRIN

Rectal delivery of drugs has been proven to be effective in terms of drug absorption and distribution comparable with other routes such as oral, buccal, sublingual or even nasal. In this study, two new suppository bases were developed using combinations of locally sourced hydrogenated palm kernel oil, hydrogenated palm kernel stearin and hydrogenated palm kernel olein with mixtures of stearic acid and glyceryl monostearate. When formulated with aspirin, these bases produced suppositories with acceptable characteristics. These aspirin suppositories were tested on twelve healthy subjects after an approval from the Medical Ethics Committee, University of Malaya had been procured. We quantified aspirin from the urine samples of the subjects to determine the relative availability of the different suppository preparations relative to an oral dose. The excretion of salicylic acid, one of the metabolite of aspirin in human urine taking aspirin was quantified. The F value was found to range from 1.16 to 1.38. Hence, the excretion results showed that these palm kernel oil blends are suitable suppository bases.

Robustness of Palm Kernel Oil Blend in Suppository Preparation Using Acetaminophen as a Model Drug

Background: Theobroma oil suppository base has good characteristics for the delivery of most drugs, but its polymorphism renders it a difficult medium with which to work. Preparation of suppositories using theobroma oil must be carried out at a temperature below 36 °C to avoid formation of metastable polymorphs. Substitutes for theobroma oil are therefore desirable. Objective: To compare the characteristics of theobroma oil- and palm kernel oil blend (PKOB)-based suppositories, each produced by 2 different techniques of preparation. Methods: Theobroma oil and PKOB (consisting of hydrogenated palm kernel oil and hydrogenated palm kernel stearin in an 8:2 ratio, with 5% stearic acid and 5% glyceryl monostearate) were used as a base. Suppositories were prepared by 2 different techniques, with acetaminophen used as the model drug. The standard technique used a water bath to melt the base preparation at 36 °C before incorporation of acetaminophen, while the second technique involved melting the base in an oven at 60 °C. The 2 types of suppositories produced by these techniques were then tested physically for appearance, hardness, liquefaction time, and melting characteristics using differential scanning calorimetry. Results: Satisfactory theobroma oil–based suppositories were produced by the water bath technique at 36 °C, but the oven technique at 60 °C failed to produce a good product. On the other hand, both techniques produced satisfactory PKOB-based suppositories that were similar in both physical and thermal characteristics. Conclusions: PKOB constituted with the above-mentioned ingredients can be exposed to a wider range of temperatures without risk of polymorphism.

アミノ酸とラウリン酸を利用した安全性の高い吸収改善製剤の開発：アミノ酸によるCytoprotectionとその機構

The development of combinatorial chemistry and high-throughput screening techniques has made it possible to generate many new drug candidates very rapidly, but it has also resulted in a number of poorly soluble and/or poorly absorbable candidates. A new trend in drug development based on pharmacogenomics or the development of molecular-targeted drugs is also spurring the tendency, and it does not necessarily lead to good output in terms of the development of new drugs. It is attractive to improve membrane permeability as well as solubility by using adjuvants, because this method could be applicable for various drugs. However, the practical use of absorption-enhancing adjuvants has been limited because of the potential local toxicity. Therefore suppressing the potential local toxicity would lead to the successful development of safe preparations with improved absorption using adjuvants. Our biochemical and histopathologic studies showed that several amino acids such as taurine and L-glutamine had cytoprotective activity, and it has been found that the combinatorial use of sodium laurate (C12) with these amino acids could maintain the absorption-enhancing ability of C12. A suppository preparation containing C12 and taurine remarkably improved the rectal absorption of rebamipide, classified as BCS class IV, and the preparation was safe to the rectal mucosa. For the mechanisms of cytoprotective action by these amino acids, it has been found that they suppress the intracellular calcium level, induce the expression of heat-shock protein 70, and inhibit the release of histamine and apoptosis.

A Meta-Analysis of the Placebo Rates of Remission and Response in Clinical Trials of Active Ulcerative Colitis

Knowledge of the placebo outcomes and understanding specific study features that influence these outcomes is important for designing future clinical trials evaluating therapy of ulcerative colitis (UC). The aims of this study were to estimate the placebo rates of remission and response in placebo-controlled, randomized clinical trials for active UC and to identify factors influencing these rates. We performed a systematic review and meta-analysis of placebo-controlled, randomized clinical trials evaluating therapies for active UC identified from MEDLINE from 1966 through 2005. Forty studies met the inclusion criteria. The pooled estimates of the placebo rates of remission and response were 13% (95% confidence interval, 9%-18%; range, 0%-40%; median, 12%) and 28% (95% confidence interval, 23%-33%; range, 0%-67%; median, 30%), respectively, both with significant heterogeneity. Studies that used more stringent definitions of outcomes had lower placebo rates of remission and response. Study duration, number of study visits, disease duration, baseline composite and rectal bleeding scores of the disease activity index, and inclusion of endoscopic mucosal healing as the remission definition all were associated with the placebo remission rate. Rates of remission in the placebo arm of UC clinical trials ranges from 0% to 40%. The placebo remission rates are influenced by the trial length, number of study visits, use of stricter remission definitions, and design features that enroll patients with more active disease. These factors should be considered when designing future placebo-controlled clinical trials in patients with active UC.

Diclofenac Sodium in the Treatment of Osteoarthritis

Diclofenac is a well-tolerated, traditional nonsteroidal anti-inflammatory drug that has been shown to be very effective for the treatment of osteoarthritis. Serendipitously, diclofenac has been shown to be relatively selective for cyclooxygenase-2; perhaps due to that fact, it has proven to be well tolerated. Tolerance and utility have been augmented with a variety of formulations, including extended-release tablets, a combination tablet with misoprostol, a suppository preparation and a topically absorbed solution. Sodium diclofenac tablets are available in 25 and 50 mg units, the extended-release tablets are available in 75 and 100 mg units, and the suppositories in 50 and 100 mg units. The usual daily dose ranges from 75 to 150 mg, ingested as two or three divided doses. The drug is a phenylacetic acid derivative. Although it is completely absorbed, only 60% is thought to reach the systemic circulation due to first-pass metabolism. The area under the plasma concentration curve is proportional to the dose in the range of 25–150 mg.

Optimization of Suppository Preparation Containing Sodium Laurate and Taurine That Can Safely Improve Rectal Absorption of Rebamipide

We previously reported that the fatty base suppository containing sodium laurate (C12) and taurine (Tau) (C12-Tau suppository) could enhance the colonic absorption of rebamipide, a poorly water-soluble and poorly absorbable drug, without any serious mucosal damages in rats. In the preset study, in order to make C12-Tau suppositories available for practical use, the scaling-up studies of animal and formulation size were performed, compared with the suppositories containing sodium caprate (C10) (C10 suppository) at the same amounts as those contained in the commercial products. Twenty-mg C12 improved the dissolution of rebamipide from suppository remarkably and the addition of 30-mg Tau only slightly decreased the dissolution rate. The absorption of rebamipide from rabbit rectum was more markedly improved by suppositories containing C12 than C10 suppositories. Although Tau tended to attenuate the absorption-enhancing effect of C12, several C12-Tau suppositories kept high bioavailability values, which were much higher than control. Histopathological studies showed that Tau exerted the cytoprotective action and that C12-Tau suppositories were better than C10 suppositories in safety. Considering the balance between efficacy and safety, the suppository containing 10- or 20-mg C12 with 30-mg Tau is better than C10 suppositories as commercial products and could be promising for practical use in human.

Role of Mesalazine in Acute and Long-Term Treatment of Ulcerative Colitis and Its Complications

Background : Sulfasalazine, consisting of 5-aminosalicylic acid bound to sulfapyridine by a diazo bond, was first used for treatment of ulcerative colitis in the early 1940s and later found effective in placebo-controlled trials for acute disease and for long-term maintenance of remission. Later studies found that the active moiety is 5-ASA (mesalazine, mesalamine) and the sulfapyridine moiety acts as a carrier molecule but causes many of the symptomatic adverse reactions. Methods : Review of the literature. Results : The finding that 5-ASA in the active motility led to the development of mesalazine prodrugs, olsalazine (Dipentum ® ) and balsalazide (Colazide ® Colazal ® ), and targeted release mesalazine preparations, such as Asacol ® Pentasa ® and Salofalk ® as well as enemas and suppository preparations for distal disease. Most patients with adverse effects from sulfasalazine will tolerate mesalazine. Mesalazine has been shown equivalent or superior to sulfasalazine, and superior to placebo, with a dose-response benefit, in inducing remission of acute disease, and comparable to sulfasalazine and superior to placebo for long-term maintenance of remission. Better tolerance of mesalazine and the ability to use higher doses favor its use in patients intolerant of sulfasalazine and in patients failing to respond to usual doses of sulfasalazine. Adverse effects from mesalazine are uncommon, but include idiosyncratic worsening of the colitis symptoms and renal toxicity. Mesalazine is safe to use during pregnancy and for nursing mothers. As maintenance therapy, mesalazine may reduce the risk of developing colorectal carcinoma. Conclusion : Mesalazine represents effective and well-tolerated first-line therapy for mildly to moderately acute disease as well as for the long-term maintenance treatment in the patient with ulcerative colitis.

Application of curdlan to controlled drug delivery. III. Drug release from sustained release suppositories in vitro.

The use of curdlan, a natural beta-1,3-glucan, in the preparation of sustained release suppositories was studied in vitro. To prepare the suppositories, indomethacin, prednisolone or salbutamol sulfate was mixed with curdlan gel. Preparation conditions, including heating time and curdlan concentrations of 5 and 10%, had little effect on the drug release. The tonicity (hypotonic or isotonic) of the media for the suppository preparation and for in vitro drug release study also had little effect on drug release. However, the heating temperature during gel preparation, the drug amount in the suppository and the type of release media did affect drug release. It was found that drug release was sustained and diffusion-controlled in the three drugs. And finally, curdlan can be applicable for use in a sustained release suppository.