Suppository Formulations Research Articles

Assessment of Efficiency and Safety of Phytocomposition with Prostate-Protective Properties in the form of Rectal Suppositories

Assessment of Efficiency and Safety of Phytocomposition with Prostate-Protective Properties in the form of Rectal Suppositories

Development of a rectally administrable Dnase1 to treat septic shock by targeting NETs

AimsNeutrophil extracellular trap (NET), which is formed by DNA threads, induces septic shock by aggravating systemic inflammation. An intravenous administration of deoxyribonuclease is regarded as a compelling modality for treating septic shock. However, alternative routes should be chosen when cutaneous veins are all collapsed due to hypotension. In this study, we genetically engineered this enzyme to develop a rectal suppository formulation to treat septic shock. Main methodsDnase1 was mutated at two amino acid residues to increase its stability in the blood and fused with a cell-penetrating peptide CR8 to increase its absorption through the rectal mucosa, which is designated AR-CR8. The life-saving effect of AR-CR8 was evaluated in a LPS-induced shock mouse model. Key findingsAR-CR8 was shown to remove NETs effectively in human neutrophils. When AR-CR8 was administered to the mouse rectum, the deoxyribonuclease activity in the mouse serum was significantly increased. In the LPS-induced shock model, 90 % of the control mice died over 72 h after LPS injection. In contrast, the rectal administration of AR-CR8 showed a mortality rate of 30 % by 72 h after LPS injection. The Log-rank test revealed that the survival rate is significantly higher in the AR-CR8 group. The NET markers in the mouse serum were enhanced by LPS, and significantly downregulated in the AR-CR8 group. These results suggest that AR-CR8 ameliorates LPS-induced shock by degrading NETs. SignificanceThe engineered DNASE1 could be developed as a rectal suppository formulation to treat septic shock urgently at out-of-hospital places where no syringe is available.

Удосконалення комплексного підходу до лікування функціональних закрепів у дітей

Functional constipation in children has become a serious medical issue that needs to be addressed immediately. They can significantly limit children’s physical activity and social integration, which emphasizes the importance of providing them with effective care. Purpose - to analyze and improve the results of the complex use of a lactulose-based drug and prophylactic phytocylinders with a lipophilic complex of rose hips and chamomile extract in the treatment of functional constipation in children. Materials and methods. We examined 78 children with constipation over the past 3 years. They were divided into two groups. The first group included 36 (46.2%) patients, the second - 42 (53.8%). Patients of the first group received standard treatment according to the protocols of the Ministry of Health of Ukraine, patients of the second group received similar treatment and additionally lactulose in the form of syrup and a preparation based on prophylactic phytocylinders with a lipophilic complex of rose hips and chamomile extract during the course of treatment daily in the form of rectal suppositories. Results. Most patients were female (60.2%), had average physical development parameters. The duration of constipation ranged from 1 to 3 months, and stool retention - from 3 to 5 days. At the beginning of the observation, there were complaints of changes in the shape and consistency of stools, painful defecation, flatulence, periodic abdominal pain, strong straining during defecation, fear or anxiety in children before the act of defecation. An analysis of anamnestic data showed that in one third of patients, constipation was observed during the transition from breastfeeding to artificial feeding. Conclusions. The analysis of the addition to the complex of treatment of functional constipation, in addition to lactulose, of preparations based on prophylactic phytocylinders with a lipophilic complex of rose hips and chamomile extract is a safe and quite effective method of correcting these disorders in young children, as evidenced by the results obtained. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

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.

ANALYSIS OF T-CELL IMMUNITY IN WOMEN WITH VAGINAL MICROBIOTA DISORDERS UNDER COMPLEX TREATMENT

Introduction. Immunological aspects of vaginal microbiota encompass the state of humoral and cellular immunity, which serves the primary function of nonspecific immune system stimulation. Therefore, alterations in its species composition lead to numerous disruptions in both cellular and humoral immune responses. The aim of the study – to investigate the parameters of T-cell immunity in women of reproductive age with vaginal microbiota disorders. Research Methods. We examined 115 women of reproductive age with vaginal microbiota disorders. To treat bacterial vaginosis in the third group of women according to the “Anomalous Vulvovaginal Discharge” treatment protocol, we selected the antibiotic metronidazole. In the second group with an intermediate type of vaginal microbiota, probiotics containing live Lactobacillus casei IMB B-7280 strains in the form of capsules and suppositories were used to normalize the species composition. After applying comprehensive therapy, we assessed the indicators of T-cell immunity in the study groups before treatment and one month after treatment. Results and Discussion. When studying T-cell immunity in women of reproductive age with vaginal microbiota disorders, no statistically significant changes in the levels of T-cells (CD3+, CD19-), T-helpers (CD4+, CD8-), and T-suppressors/T-cytotoxic cells (CD4-, CD8+) were found within the reference norms. However, statistically significant differences in T-suppressors/T-cytotoxic cells (CD4-, CD8+) were observed before treatment depending on the study groups. The lowest statistically significant level of these cells was found in the group of women with bacterial vaginosis, but the indicators of this immune branch tended to increase compared to the control group after complex treatment. After probiotic therapy, there was a tendency to increase T-helpers (CD4+, CD8-) in women with an intermediate type of vaginal microbiota. Conclusions. In conclusion, the analysis of the studied parameters of cellular immunity in women with vaginal microbiota disorders revealed a statistically significant decrease in T-suppressors/T-cytotoxic cells (CD4-, CD8+), which deepened as the vaginal microbiota disorder progressed. This indicates the influence of the species composition of vaginal microbiota on the T-suppressor/T-cytotoxic cellular immune branch.

Treatments and Management of Menopausal Symptoms: Current Status and Future Challenges

In the United States (US), menopause occurs at an average age of 52. Menopausal symptoms tend to be maximal during the few years before and the year after menopause (during perimenopause), except for symptomatic vulvovaginal atrophy, which may worsen over time. Up to 20% of bone density loss occurs during the first 5 years after menopause, followed by an age-related bone loss rate similar to that in men. Menopause should be considered confirmed if an age-appropriate woman who is not pregnant has not had a menstrual period for 12 months. Regarding treatment, for vaginal dryness or dyspareunia due to menopause, vaginal stimulation and vaginal lubricants and moisturizers are recommended, and if these are ineffective, low-dose vaginal estrogen, in the form of creams, tablets, suppositories, or rings should be considered; other options include oral ospemifene or intravaginal dehydroepiandrosterone (DEHA) suppositories. Before prescribing hormone replacement therapy (HRT) and periodically while therapy continues, women should be informed of risks (e.g., deep vein thrombosis [DVT], pulmonary embolism [PE], stroke, breast cancer, gallbladder disease, and urinary incontinence); potential harms are greatest for women who start HRT after 60 years of age or who are 10-20 years past menopause onset. If women choose HRT to relieve hot flushes, estrogen plus, a progestin or conjugated estrogen/bazedoxifene could be prescribed for women who still have the uterus. Treatment with HRT should be tailored to maximize benefits and minimize harms, and periodically benefits and harms should be reassessed; low-dose transdermal HRT may lead to a lower risk of DVT and stroke. Selective serotonin reuptakereuptake inhibitors (SSRIs), selective serotonin-nor-epinephrine reuptake inhibitors (SNRIs), and gabapentin could be considered as less effective alternatives to HRT for relieving hot flushes; paroxetine 7.5 milligrams (mg) is the only non-hormonal drug approved in the US for the relief of hot flushes. Effective non-drug options include cognitive behavioral therapy and hypnosis.

Evaluation of the clinical efficacy of the use of oxidized dextran in the form of suppositories in the treatment of patients with chronic prostatitis

BACKGROUND: Increasing the efficacy of treatment of patients with chronic prostatitis / chronic pelvic pain syndrome remains an urgent problem of modern urology.
 AIM: The aim of the study is to evaluate the clinical efficacy of rectal suppositories with oxidized dextran in the treatment of patients with chronic prostatitis / chronic pelvic pain syndrome.
 MATERIALS AND METHODS: 52 patients with chronic prostatitis / chronic pelvic pain syndrome were treated (mean age 33.1 1.7 years). The patients were divided into 2 groups. Patients of the 1st group (n = 25) received oxidized dextran in the form of rectal suppositories for 50 days according to the following scheme: for the first 10 days, 1 rectal suppository at night, daily; the next 40 days 1 rectal suppository every other day. A total of 30 rectal suppositories per course. Patients of the 2nd group (n = 27) received a placebo in the form of rectal suppositories according to the same scheme. Treatment efficacy was assessed on the basis of the original IPPS-MS Genitourinary Disease Assessment questionnaire, the NIH-CPSI and IIEF-5 questionnaires, as well as the results of microscopic examination of prostate secretions.
 RESULTS: In patients of the 1st group a significant clinical improvement was revealed by the end of treatment. According to the IPPS-MS questionnaire there was a decrease in the severity of dysuria by 67%, pain syndrome by 80%, psychosomatic disorders by 47.6%. There was a decrease in the total score of the NIH-CPSI questionnaire by 66.2% (from 25.4 2.4 to 8.6 2.1 points, p 0.05) and an increase in the total score of the IIEF-5 questionnaire by 79.3 % (from 11.6 1.8 to 20.8 2.1 points, p 0.05). Positive changes in the clinical parameters of patients of the 1st group were accompanied by an improvement in the results of microscopy of the secretion of the prostate a decrease in the number of leukocytes and an increase in the number of lecithin grains. There were no significant changes in any of the studied parameters in patients of the 2nd group. None of the patients in both groups had side effects from the therapy.
 CONCLUSIONS: Oxidized dextran in the form of rectal suppositories has a pronounced anti-inflammatory activity and significantly reduces the severity of dysuria, pain and psychosomatic disorders in patients with chronic prostatitis / chronic pelvic pain syndrome. The results of the study indicate the promise of using oxidized dextran in the form of rectal suppositories for the treatment of patients with chronic prostatitis / chronic pelvic pain syndrome.

Development of optimal in vitro release and permeation testing method for rectal suppositories

Currently there are no compendial assays for testing drug release from rectal suppositories. It is therefore essential to study different in vitro release testing (IVRT) and in vitro permeation testing (IVPT) methods for identifying a suitable technique to compare in vitro drug release and to predict in vivo performance of rectal suppositories. In the present study, three different rectal suppository formulations of mesalamine (CANASA, Generic, and In-house) were studied for in vitro bioequivalence. All the different suppository products were characterized by performing weight variation, content uniformity, hardness, melting time, and pH tests. Viscoelastic behavior of the suppositories was also tested both in presence and absence of mucin. Four different IVRT techniques such as Dialysis, Horizontal Ussing Chamber, Vertical Franz cell, and USP apparatus 4. IVPT studies were performed using Horizontal Ussing chamber and Vertical Franz cell methods. Q1/Q2 equivalent products (CANASA, Generic) and a half-strength product were studied to understand the reproducibility, bio relevance, and discriminatory ability of the IVRT and IVPT methods. This study is the first of its kind where molecular docking studies were performed to determine the potential interactions of drug (mesalamine) with mucin, IVRT studies were conducted with and without the presence of mucin, and porcine rectal mucosa was used to perform IVPT tests. The USP 4 method and Horizontal Ussing chamber methods were found to be suitable IVRT and IVPT techniques, respectfully, for rectal suppositories. RLD (Reference Listed Drug) and Generic rectal suppositories were found to exhibit similar release rate and permeation profiles obtained from USP 4, and the IVPT studies, respectfully. Wilcoxon Rank Sum/Mann-Whitney rank test, conducted for the IVRT profiles obtained using USP 4 method, proved the sameness of RLD and Generic suppository products.

Preclinical Potential of Probiotic-Loaded Novel Gelatin-Oil Vaginal Suppositories: Efficacy, Stability, and Safety Studies.

The current study describes a suppository base composed of aqueous gelatin solution emulsifying oil globules with probiotic cells dispersed within. The favorable mechanical properties of gelatin to provide a solid gelled structure, and the tendency of its proteins to unravel into long strings that interlace when cooled, lead to a three-dimensional structure that can trap a lot of liquid, which was exploited herein to result in a promising suppository form. The latter maintained incorporated probiotic spores of Bacillus coagulans Unique IS-2 in a viable but non-germinating form, preventing spoilage during storage and imparting protection against the growth of any other contaminating organism (self-preserved formulation). The gelatin-oil-probiotic suppository showed uniformity in weight and probiotic content (23 ± 2.481 × 108 cfu) with favorable swelling (double) followed by erosion and complete dissolution within 6 h of administration, leading to the release of probiotic (within 45 min) from the matrix into simulated vaginal fluid. Microscopic images indicated presence of probiotics and oil globules enmeshed in the gelatin network. High viability (24.3 ± 0.46 × 108), germination upon application and a self-preserving nature were attributed to the optimum water activity (0.593 aw) of the developed composition. The retention of suppositories, germination of probiotics and their in vivo efficacy and safety in vulvovaginal candidiasis murine model are also reported.

Development and Stability of a New Formulation of Pentobarbital Suppositories for Paediatric Procedural Sedation.

Pentobarbital is a drug of choice to limit motion in children during paediatric procedural sedations (PPSs). However, despite the rectal route being preferred for infants and children, no pentobarbital suppositories are marketed, and therefore they must be prepared by compounding pharmacies. In this study, two suppository formulations of 30, 40, 50, and 60 mg of pentobarbital sodium were developed using hard-fat Witepsol® W25 either alone (formulation F1) or with oleic acid (formulation F2). The two formulations were subjected to the following tests described in the European Pharmacopoeia: uniformity of dosage units, softening time, resistance to rupture, and disintegration time. The stability of both formulations was also investigated for 41 weeks of storage at 5 ± 3 °C using a stability-indicating liquid chromatography method to quantify pentobarbital sodium and research breakdown product (BP). Although both formulae were compliant to uniformity of dosage, the results were in favour of a faster disintegration of F2 compared to F1 (-63%). On the other hand, F1 was found to be stable after 41 weeks of storage unlike F2 for which several new peaks were detected during the chromatographic analysis, suggesting a shorter stability of only 28 weeks. Both formulae still need to be clinically investigated to confirm their safety and efficiency for PPS.

Возможности профилактики инфекционных осложнений при выполнении малых хирургических вмешательств в гинекологии

Aim: to evaluate the efficacy of an antiseptic disinfectant containing benzyl-dimethyl-[3-(tetradecanoylamino)propyl] ammonium chloride as an active ingredient in the form of vaginal suppositories as a preoperative management for scheduled surgery in women with vaginal microbiocenosis disorder. Patients and Methods: a prospective open-label study of the prevention of postoperative complications in 58 women admitted to a gynecological short-stay unit was conducted. The initial examination included history taking, comprehensive clinical and laboratory examinations, bacterioscopy of cervical and vaginal discharge with Gram stain, and vaginal discharge pH measurement. Surgery (diagnostic dilation and curettage along with hysteroscopy for endometrial hyperplasia) was scheduled in all women. 8.0±1.0 days before surgery, preoperative treatment to prevent infectious complications was performed using benzyl-dimethyl-[3-(tetradecanoylamino)propyl] ammonium chloride monohydrate in the form of 15-mg vaginal suppositories (1 suppository), once daily for 7 days. 30 days after surgery, re-examination of vaginal microflora and microbiocenosis was performed in all women. Results: an increase in WBC count, mixed microflora, and Candida spores were detected at the first visit. Before preventive treatment, vaginal microbiocenosis was characterized by a decrease in the number of obligate microbes in the vaginal biotope. No infectious postoperative complications were reported, and the early and late postoperative period was uneventful. In 56 women (96.5%), normocenosis was revealed (19 women were previously diagnosed with bacterial vaginosis, 25 with candidiasis, and 12 with nonspecific vaginitis). Two women (3.5%) had intermediate-type vaginal microbiocenosis. In 54 women (93.1%), the preparation was well-tolerated, while 4 women (6.9%) complained of short-term burning. Conclusions: the preparation can be recommended as a preventive antiseptic agent before scheduled minor gynecological surgeries in women with vaginal microbiocenosis disorder. KEYWORDS: minor gynecological surgeries, postoperative infectious inflammatory complications, prevention, vaginal microflora, hysteroscopy, antiseptic agent. FOR CITATION: Khlynova S.A., Dobrokhotova Yu.E., Kerchelaeva S.B., Fisenko A.D., Dimitrova V.I. Prevention of infectious complications in minor gynecological surgeries. Russian Journal of Woman and Child Health. 2023;6(3):270–275 (in Russ.). DOI: 10.32364/2618-8430-2023-6-3-9.

The Improvement of the Dissolution and Release Characteristics of Ibuprofen Suppository Through Inclusion Complexes with

Ibuprofen is classified as a BCS class II because of its low solubility and high permeability. Inclusion complex formation using β-cyclodextrin is one method to increase a drug’s solubility. In addition to the method of increasing the solubility, the choice of dosage form and route of administration has a big role in the success of therapy because it can increase the onset of action of drugs while avoiding side effects. Rectal suppositories can provide a faster antipyretic effect than oral preparations. The purpose of this study was to determine the effect of inclusion complexes formation with β-cyclodextrin in increasing the dissolution rate and release characteristics of ibuprofen suppositories. The suppository formulation used various concentrations of cetylalcohol to increase the consistency of the cocoa butter base. The release characteristics of ibuprofen in suppositories were evaluated, including, organoleptic, melting time, weight diversity, dissolution rate and dissolution efficiency, by comparing ibuprofen inclusion complex suppositories with β-cyclodextrin all three mole ratios, namely 1:1, 1:2 and 2:1, to pure ibuprofen suppositories. The inclusion complex of ibuprofen with β-cyclodextrin at a mole ratio of 2:1 showed to increase the solubility and dissolution rate of ibuprofen in suppositories with good physical and release characteristics.
 Keywords: ibuprofen, inclusion complexes, suppository

Development of Suppositories Silicone Molds Using Additive Technologies

Introduction. In modern practice, suppositories are prepared by hand rolling method or fusion. 3D printing can overcome the disadvantages of traditional suppository manufacturing methods and solve the problems of personalization. 3D printing makes it possible to manufacture drug-loaded suppositories without the use of molds or other physical support. The current studies have a number of limitations, and the printing of one suppository requires a long time. This report proposes a method of 3D modeling and 3D printing to produce personalized suppositories by fusion.Aim. Various sizes and shapes suppositories silicone molds development by molding method from hydrophilic, lipophilic and amphiphilic bases.Materials and methods. Suppository bases: cocoa butter (Luker, Colombia), polyethylene glycol (PEG) 1500 (Merck KGaA, Germany), PEG-400 (Merck KGaA, Germany), Witepsol H-15 (Chimmed Group, Russia); pharmaceutical substance: paracetamol (Hebei Jiheng (Group) Pharmaceutical Co. Ltd, China); filaments for 3D printing: polyethylene terephthalate (PET-G natural, LLC "PrintProdakt", Russia); silicone two-component platinum, hardness Shore 30A (China); solvents: Acetonitrile Grade HPLC (Merck KGaA, Germany). The design of the both casting and master molds of suppositories was carried out using the KOMPAS-3D version 17.1. Master molds were printed by Picaso PRO 250 and Picaso X Pro 3D printers. Mold segments were obtained by filling master molds with a mixture of two-component silicone. Suppositories were obtained by molding method. Their average weight and standard deviation were determined. Paracetamol concentration in suppositories was carried out by UV spectrophotometry on a UV-1240 mini spectrophotometer (Shimadzu, Япония). Silicone molds were soaked and washed in hot water with surfactants. Washouts from the molds were taken by soaking the mold.Results and discussion. The torpedo-shaped form was chosen as the model form of suppositories. For the chosen form, three volumes of suppositories were designed: 3.32 ml; 1.5 ml and 0.25 ml. Silicone molds were designed and manufactured for all volumes. The cast suppositories were examined for compliance with the regulatory documentation for the dosage form, the average weight and mass uniformity were evaluated. Suppositories with paracetamol were made. A procedure for cleaning the obtained silicone molds has been developed.Conclusion. The resulting silicone molds make it possible to obtain suppositories in accordance with the regulatory documentation for the suppositories. Silicone molds have significant advantages compared to analogues of metal or polymeric molds.

Complex treatment of patients with chronic bacterial prostatitis using biologically active peptides

BACKGROUND: Increasing the effectiveness of the treatment of chronic bacterial prostatitis is an actual problem of modern urology.
 AIM: The aim of the study was to study the effectiveness of complex treatment of patients with chronic bacterial prostatitis using Prostatex.
 MATERIALS AND METHODS: This study included 94 patients with chronic bacterial prostatitis aged 21 to 45 years. Patients of group I (n = 47) received standard antibiotic therapy (levofloxacin at a dose of 500 mg 2 times a day for 28 days), and patients of group II (n = 47) received standard antibiotic therapy combined with the prescription of Prostatex in the form of rectal suppositories 10 mg once a day.
 RESULTS: The overall clinical efficacy of treatment in patients of group II was 2 times higher than in patients of group I. After treatment in patients of group II compared with group I a statistically significant decrease in chronic bacterial prostatitis symptoms according to the NIH-CPSI and IPSS questionnaires was recorded. Eradication of microflora in 91.4% of patients of group II was achieved, there was a significant decrease in prostate volume, an increase in the average volumetric flow rate of urine by 89.8%, normalization of perfusion parameters and the index of microcirculation efficiency.
 CONCLUSIONS: The results of the study showed that the use of Prostatex in the complex treatment of chronic bacterial prostatitis patients has a positive effect on the main symptoms of chronic prostatitis, significantly reducing pain, urination disorders and improving sexual function. This therapy helps to reduce the volume of the prostate and the volume of residual urine, restores microcirculation in the prostate gland and can be recommended in this category of patients.

ВЛИЯНИЕ КИСЛЫХ И ЩЕЛОЧНЫХ СРЕД НА ВРЕМЯ ПЛАВЛЕНИЯ ГИДРОФИЛЬНЫХ И ЛИПОФИЛЬНЫХ СУППОЗИТОРИЕВ

Abstract. In the pharmaceutical industry, disintegration testing is one of the most important methods for the development and quality control of drugs in the form of suppositories. Once inserted into a natural body cavity, the suppositories melt, soften, or dissolve in the rectal fluid and produce localized or systemic effects. The results of the active development of the excipients industry and the dynamics of the pharmaceutical ingredients market, the success of pharmaceutical technology, new principles of quality regulation dictate the need to analyze and generalize the current trends in the production of this dosage form. The purpose of this study is to show the effect of acidic (pH=4) and basic (pH=6) solvents on the melting time of both hydrophilic and lipophilic bases. Eleven formulas of different mixing concentrations of hydrophilic bases (polyethylene glycols) and one formula of a lipophilic base (Witepsol W37) were obtained by fusion. As a result of the experiment, it was found that the melting time of lipophilic bases (W37) was longer compared to hydrophilic bases in both acidic and basic environments. Among the hydrophilic suppositories, the formula containing PEG 4000 demonstrated a longer melting time compared to other formulas in both media. In addition, during the experiment, it was found that lipophilic bases (W37) are harder than hydrophilic ones in terms of characteristics, which may be due to including those with a higher melting point of fat-soluble than hydrosoluble suppositories. The results obtained led to the conclusion that suppositories based on hydrophilic bases (polyethylene glycol) have a shorter melting time in both acidic and basic solutions than lipophilic ones (Witepsol W37). Due to this, soluble drug compounds are more easily delivered to the site of action. That is, hydrophilic bases are more effective for the manufacture of vaginal suppositories.

Community access to rectal artesunate for malaria (CARAMAL): A large-scale observational implementation study in the Democratic Republic of the Congo, Nigeria and Uganda.

The key to reducing malaria deaths in highly endemic areas is prompt access to quality case management. Given that many severe cases occur at peripheral level, rectal artesunate (RAS) in the form of suppositories was developed in the 1990s, allowing for rapid initiation of life-saving antimalarial treatment before referral to a health facility with full case management capabilities. One randomized controlled trial published in 2009 showed a protective effect of RAS pre-referral treatment against overall mortality of 26%, but with significant differences according to study sites and length of referral. Two important issues remained unaddressed: (1) whether the mortality impact of RAS observed under controlled trial conditions could be replicated under real-world circumstances; and (2) clear operational guidance for the wide-scale implementation of RAS, including essential health system determinants for optimal impact. From 2018 to 2020, the Community Access to Rectal Artesunate for Malaria (CARAMAL) project was conducted as a large-scale observational implementation study in the Democratic Republic of the Congo (DRC), Nigeria, and Uganda (registered on ClinicalTrials.gov as NCT03568344). CARAMAL aimed to provide high-quality field evidence on the two issues above, in three remote settings with high malaria endemicity. A number of complementary study components were implemented. The core of the CARAMAL study was the Patient Surveillance System (PSS), which allowed tracking of cases of severe febrile illness from first contact at the periphery to a referral health facility, and then on to a Day 28 visit at the home of the patient. Community and provider cross-sectional surveys complemented the PSS. Here we describe in some detail RAS implementation, as well as the key CARAMAL study components and basic implementation experience. This manuscript does not intend to present key study results, but provides an extensive reference document for the companion papers describing the impact, referral process, post-referral treatment and costing of the RAS intervention.

The Outcome of Shock Wave Lithotripsy (SWL) in the Treatment of Urinary Stone Disease: 115 Cases in SOMCH

Purpose: Urinary stone disease is a systemic metabolic and recurrent disease. It is the third most common disease of the urinary tract. Urolithiasis affects 4%-15% of the world population and this is increasing. Treatment of urinary stone disease moved dramatically from open operative procedures to endoscopic, minimally invasive, and noninvasive methods. The introduction of shock wave lithotripsy (SWL) has revolutionized the treatment of urinary stones with the concept of disintegration of stones. The present study aims to evaluate the outcome of SWL in the treatment of urinary stone disease. Methods and Materials: This retrospective observational study was conducted in the department of urology, SOMCH from June 2019- to March 2021. Renal stone <2.0 cm & upper Ureteric stone <1.5 cm were included and radiolucent stones, patients having ureteral obstruction with grossly impaired renal function, UTI, uncontrolled bleeding disorder, pregnancy & BMI >30kg/m2 were excluded. A total of 115 patients was enrolled. SWL with Siemens Lithoskope (3rd generation) lithotripter was used with a standard number of shock waves 2500-3500 per session & an energy setting of 3.0-3.5 KV. NSAID was given in suppository form and intravenous pethidine just before starting shock for analgesia and all were under antibiotic prophylaxis. Patients were discharged the day after the SWL procedure with the advice of follow-up every 2 weeks for 3 months. All patients were followed up with history, urine R/M/E & C/S to detect UTI, plain X-ray KUB region to see stone clearance or any other complications. Results: Total 179 sessions of SWL procedure done for 115 patients (1.55/ patient) with the urinary stone of both gender between 19 to 70 years. Of them, 82(71.3%) were male and 33(28.7%) female and 94(81.5%) were in the 20-60 years age group. Renal stones 78(67.9%), upper ureteric stones 37(32.1%), and 70(60.8%) were on the left side. Preprocedure stenting was done in 35(30.4%) patients due to obstruction & residual stones. 70(60.9%) have achieved stone clearance after the first session of SWL. After a maximum of 3 sessions of SWL and 3 months follow up found that 99(86%) patients were stone-free. Only 16(14%) found treatment failure and needed auxiliary procedures like URS, RIRS, etc because of hard stone, steinstrasse, and patients’ non-compliance due to pain & fearlessness. 13(11.3%) patients complain of moderate pain after SWL and needed a maximum of 2 days of hospitalization with an injectable pain killer. UTI was found in 9(7.8%) patients, of the 7(6.1%) were pre-stenting. Gross hematuria was found in 2(1.7%) patients due to HDN & UTI. Conclusion: As the stone clearance rate is high with fewer complications however multiple sessions are required, SWL, a noninvasive procedure, is a good option for the treatment of urinary stone disease. Bangladesh J. Urol. 2021; 24(2): 166-169

Formulation Development of Azadirachta indica Extract as Nanosuppository to Improve its Intrarectal Delivery for the Treatment of Malaria

Previous folkloric and experimental reports have demonstrated the antimalarial efficacy of Azadirachta indica (AZA) extracts. However, one of the major challenges facing its application for the clinical treatment of malaria is the design of an acceptable dosage form. Consequently, we developed AZA extract-loaded nanostructured lipid carriers (NLC) for the formulation of suppositories, denoted as nanosuppositories, for intrarectal treatment of malaria. Various batches of NLC-bearing AZA extract were formulated based on lipid matrices prepared using graded concentrations of Softisan®154 and Tetracarpidium conophorum or walnut oil. NLC was investigated by size and differential scanning calorimetry (DSC). Suppository bearing AZA extract-loaded NLC was developed using cocoa butter or theobroma oil, and their physicochemical properties were profiled. In vitro drug release and in vivo antimalarial activity (using Plasmodium berghei-infected mice) were investigated. NLCs exhibited sizes in nanometers ranging from 329.5 - 806.0 nm, and were amorphized as shown by DSC thermograms. Nanosuppositories were torpedo- or bullet- shaped, weighing 138 - 368 mg, softened/liquefied between 4.10 - 6.92 min, and had controlled release behaviour. In vivo antimalarial study revealed excellent antimalarial efficacy of the nanosuppositories comparable with a commercial brand (Plasmotrim®) and better than the placebo (unloaded nanosuppository), and without toxic alterations of hepatic and renal biochemical factors. Thus, AZA extract could be rationally loaded in nanostructured lipid carriers (NLC) for further development as nanosuppository and deployed as an effective alternative with optimum convenience for intrarectal treatment of malaria.

The Current State and Prospects for the Use of Herbal Medicines for Wound-Healing and Anti-Inflammatory Action in Kazakhstan: A Literature Review

BACKGROUND: As dosage forms, oils, drops, ointments, solutions, films, and suppositories represent phytopreparations for external use. The use of the drug “Kyzyl mai” in clinical practice pursues the achievement of wound-healing (including anti-burn effect), anti-inflammatory, reparative, metabolic, antibacterial, antiviral, and analgesic effects. AIM: We aimed to analyze the range of soft dosage forms in the form of suppositories with herbal components in their composition, used as anti-inflammatory and wound-healing agents. METHODS: The design in this study was a literature review article. Search for articles using relevant ones obtained from data based on PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar obtained 283 articles. RESULTS: There are 12 articles that are relevant and discuss their content and use in the health. CONCLUSION: This review presents new dosage forms have been created – medicinal film “Fiadent,” medicinal film “Normophyt,” medicinal film with Piyavit. On the basis of chamomile extract obtained by supercritical carbon dioxide extraction, the optimal composition and technological scheme for the production of anti-inflammatory suppositories for use in proctology have been developed. The article describes a literature review of suppositories of anti-inflammatory action based on essential oil of balsamic poplar buds which have been developed.