Suppositories Research Articles

A randomised controlled trial to evaluate the effect of GandhakaRasayana rectal suppository in post operative pain management in ano-rectal disorders

BackgroundPoorly managed post-operative pain can lead to complications and prolonged rehabilitation. Pain Management after ano-rectal surgery becomes important as it could hamper day to day activities, disturb sleep, alter appetite and bowel evacuations and decrease the quality of life. According to Acharya Sushrutha, pain (Shoola) cannot be produced without Vata dosha and Shoola (pain) is inevitable after Shastra (surgical) Karma (procedure) for which Basti (enema) is usually the management of choice. Rectal suppositories are one such dosage form that are extensively used in post-operative pain management especially after ano-rectal surgery. Materials and methodIn the study, a total of 40 patients who fulfilled the inclusion criteria were randomly divided to two groups comprising of 20 patients each. Patients of Group A were treated with Gandhaka Rasayana rectal suppository and Group B were treated with Diclofenac Sodium rectal suppository for post-operative 5 days. ResultsThe overall comparative results revealed a statistically significant improvement of 85% in Group A and 80.39% in Group B. Gandhaka Rasayana which is Tridoshashamaka, Vatamaya Nivaraka (ameliorates diseases caused by Vata dosha), Agnivardhaka (improves appetite and metabolism) and Shoolahara (reduces pain) attains micro particle size with 88 Bhavana (trituration) that can be readily absorbed by the rectal mucosa to exhibit the required therapeutic action. ConclusionThe Bhavana Dravya (medium of trituration) used in the preparation of Gandhaka Rasayana have proven analgesic, anti-inflammatory, anti-bacterial action and is also said to promote wound healing. The present study reveals that there is significant effect of Gandhaka Rasayana rectal suppositories in managing post-operative pain of ano-rectal disorders.

Rectal indomethacin versus intraperitoneal lidocaine for analgesia after laparoscopic cholecystectomy

Background: Visceral and shoulder painare among the most frequent reported pain after laparoscopic cholecystectomy (LC). Objectives: To investigate the effectiveness and clinical value of rectal indomecthacin and intraperitoneal lidocaine for treating pain after laparoscopic cholecystectomy. Patients and methods: In Qena university hospital, this prospective randomized comparative study was conducted, 80 patients were scheduled to elective laparoscopic cholecystectomy. Group intraperitonealIP lidocaine (40 patients) received 200 ml saline containing 200 mg 2%lidocaine immediately after pneumoperitoneum, the total solution was sprayed on the upper surface of the liver, right subdiaphragmatic space and around the cholecystectomy site. Group indomethacin (40 patients) received two 100 mg indomethacin rectal suppositories 2 hours prior to surgery. Results: VAS score was significantly lower in indomethacine group ( p value =0.03)over the 24 hours postoperative . The postoperative pethidine requirements were significant lower in group indomethacin mean (34±11.4 mg). Postoperative nausea and vomiting were less in group indomethacin with no statistically significant difference. Conclusion: preoperative rectal indomethacin suppositories decrease postoperative pain scores and analgesics requirements without producing side effects comparing to IP lidocaine in LC. Clinical trail .gov . ID:NCT04964180

Development and Validation of Hplc-Dad and Lc-(Esi)/Ms Methods for the Determination of Sulfasalazine, Mesalazine and Hydrocortisone 21-Acetate in Tablets and Rectal Suppositories: In Vitro and Ex Vivo Permeability Studies

Development and Validation of Hplc-Dad and Lc-(Esi)/Ms Methods for the Determination of Sulfasalazine, Mesalazine and Hydrocortisone 21-Acetate in Tablets and Rectal Suppositories: In Vitro and Ex Vivo Permeability Studies

Отдаленные результаты цитокинотерапии у беременных с дисплазией шейки матки

Aim: to assess long-term outcomes of exogenous cytokine therapy in pregnant women with cervical intraepithelial neoplasia (CIN). Patients and Methods: this prospective study included 50 pregnant women with CIN. Women were randomized into two groups. Group 1 women (n=30, mean age 31.6±1.7 years) received vaginal suppositories with Superlymph 25 U. Group 2 women (n=20, mean age 29.8±1.4 years) received rectal suppositories with Superlymph 25 U. Cervical smear cytology (at baseline, 22 days after starting treatment, and 6 weeks after delivery), colposcopy, and cervical biopsy (at baseline and 6 weeks after delivery) were performed. Results: in group 1, cytology revealed high-grade squamous intraepithelial lesion (HSIL) in 43.3%, atypical squamous cells-cannot exclude a high-grade lesion (ASC-H) in 6.7%, and atypical squamous cells of undetermined significance (ASCUS) in 10%. In group 2, cytology revealed low-grade squamous intraepithelial lesion (LSIL) in 25%, HSIL in 45%, ASC-H in 10%, and ASCUS in 20%. After the treatment course, in group 1, a regress from HSIL to LSIL was detected in 6.7%, regress from LSIL to ASCUS in 3.3%, and regress from HSIL to ASC-H in 3.3%. In group 2, NILM was detected in 5%, a regress from HSIL to LSIL in 5%, and regress from LSIL to ASCUS in 5%. Histologically, LSIL was verified in 50% of women of both groups, CIN grade 2 in 36.7% (group 1) and 40% (group 2), CIN grade 3 in 13.3% (group 1) and 10% (group 2). Six weeks after delivery, cytological abnormalities were identified in 30 women of both groups (HSIL in 56.7% and LSIL in 43.3%). Histology detected carcinoma in situ in 3.3% and CIN grade 2–3 in 53.3%. Delivery in time (on average, at 38.4±1.1 weeks of gestation) occurred in all women. Conclusion: trend toward the improvement of cytological parameters irrespective of the mode of drug administration is reported after finishing cytokine therapy. Normalization of cytological findings was reported in 3.3% (group 1) and 5% (group 2), while improvement was reported in 6.6% (group 1) and 10% (group 2). No worsening was reported.

Efficacy of Chymotrypsin in the Prevention of Postendoscopicretrograde Cholangiopancreatography Pancreatitis

Introduction: Pancreatitis is common after endoscopic retrograde cholangiopancreatography (ERCP).To assess the pharmacological effect of diclofenac, allopurinol and chymotrypsin in the prevention of post ERCP pancreatitis (PEP). Calcular obstructive jaundice patients without pancreatitis scheduled for ERCP were randomized into three groups. Methods: The diclofenac group received 200mg rectal suppositories immediately after ERCP, allopurinol received oral 300mg 3 h before ERCP, and chymotrypsin received intramuscular injection immediately after ERCP. Serum amylase and lipase were measured before, 1, 6, and 24 h after ERCP and procedure-related risk factors for post-ERCP pancreatitis were recorded. Pancreatitis was considered when serum amylase or lipase levels elevated more than three times the upper limit of normal with newly developed abdominal pain lasting at least 24 h after ERCP. Results: 150 patients were included; diclofenac group (58 patients, 29 men, mean age 46.9±13.2 years), allopurinol (38 patients, 20 men, mean age 43.1±14.7 years) and chymotrypsin (54 patients, 28 men, mean age 40.6±17.3 years). 12 (8%) patients developed PEP: the diclofenac group (n=4; 6.9%), allopurinol (n=6; 15.8%) while chymotrypsin (n=2; 3.7%), but this was not statistically significant (P=0.318). In patients who received chymotrypsin, regression of serum amylase and lipase to normal levels was much better compared with the other groups and was associated with better clinical improvement. Conclusion: Chymotrypsin and allopurinol are comparable to diclofenac in the prevention of pancreatitis post-ERCP. Beside its prophylactic role, chymotrypsin could be effective in rapid improvement if PEP occurs.

Biological Evaluation of Medical Devices in the Form of Suppositories for Rectal and Vaginal Use

Background. Programs of preclinical safety studies of the health care products depend on the regulatory status of the investigated products. The classification of such products, in particular suppositories for rectal and vaginal use, is a critical step of developing tactics for their biological evaluation. Adaptation of biological evaluation methods for the medical devices based on the combination of biologically active substances, as well as evaluation of the results of such studies is urgent task of biomedicine. Objective. To substantiate the regulatory status and to carry out a biological evaluation of medical devices in the form of vaginal suppositories based on octenidine dihydrochloride ("Prodexyn") and in the form of rectal suppositories based on Saw palmetto, Levisticum officinale and Calendula officinalis extracts ("Pravenor"). Methods. Biological evaluation was conducted according to the requirements of ISO 10993 standards using in vitro and in vivo biological test systems (cytotoxicity in cell culture and the MTT test, sensitizing and irritating effect in guinea pigs). Results. The cytotoxicity (СС50) of the medical device "Prodexyn" extract in Vero cell culture was 8.35 μg/ml calculated as octenidine dihydrochloride and 416.65 μg/ml calculated as dexpanthenol. "Pravenor" medical device was found to be non-toxic in Vero cell culture. According to the results of MMT assay CC50 for octenidine dihydrochloride was 1.67 μg/ml, and 83.33 μg/ml – for dexpanthenol. CC50 indicators calculated for the different active ingredients of the medical device "Pravenor" were the following: 50 mg/ml for the dwarf palm berries extract (Saw palmetto), 16.67 mg/ml for the lovage roots extract (Levisticum officinale), and 16.67 mg/ml for the calendula flowers extract (Calendula officinalis). No sensitizing or skin irritating effects were observed in guinea pigs. Conclusions. Biological evaluation of medical devices in the form of rectal suppositories "Pravenor" and vaginal suppositories "Prodexyn" performed using in vitro and in vivo biological systems. It was demonstrated an acceptable level of safety of the products. The MTT test was 5 times more sensitive than the Vero cell culture method in determination of cytotoxicity.

The effectiveness of combined topical product with fluocortolone pivalate and lidocaine for hemorrhoids: results of a multicenter observational study

AIM: to assess the changes in hemorrhoids symptoms and satisfaction with treatment against the background of treatment with a combined topical product Relief® Pro.PATIENTS AND METHODS:multicenter prospective non-interventional cohort study was done in 13 clinical centers in Russia. The study included patients aged 18 to 65 years with acute hemorrhoids of stages 1–2 treated with the combined product Relief® Pro (rectal suppositories, cream or a combination thereof). The follow-up period was up to 14 days (in the case of 2 visits to the clinical center after receiving the initial data). The analysis was performed on the basis of data obtained at Visit 2 (5–7 days of therapy) and Visit 3 (10–14 days of therapy) vs the initial data (Visit 1). Following criteria were used: the severity of hemorrhoid symptoms on the Sodergren scale, the severity of hemorrhoid symptoms (pain, bleeding, itching, edema, the presence of discharge, a feeling of discomfort), the size of the largest hemorrhoid node, the satisfaction of the doctor and the patient with treatment, assessment of the patient’s adherence to recommendations for lifestyle changes and treatment, evaluation of the use of the drug Relief® were evaluated as endpoints About the treatment process and patient preferences regarding the dosage form of the prescribed drug. In addition, adverse events were evaluated.RESULTS: the study included 1000 patients aged 18 to 65 years (men — 54.5%, women — 45.5%) Patients had grade 1 acute hemorrhoids (330 patients), grade 2 acute hemorrhoids (345 patients) and exacerbation of chronic hemorrhoids (325 patients). The drug Relief® Pro rectal cream was used by 333 patients; suppositories — 383 patients; joint therapy with both dosage forms — 284 patients. During follow-up (visits 2 and 3), positive dynamics was observed in patients — a decrease in the severity of hemorrhoid symptoms both during objective examination and according to patient questionnaires. So, according to the patients’ estimates, the use of Relief® Pro, regardless of the form, led to a decrease in the severity or disappearance of the main symptoms of hemorrhoids — bleeding, itching, edema, the presence of discharge, discomfort already by Visit 2 and in almost all patients by the end of observation. A similar change of the symptoms due the digital examination: by day 5–7, the severity of edema and bleeding in the perianal region, bleeding decreased. About 96% of patients and about 97% of doctors were satisfied with the treatment. Application of both forms of Relief® The ABM was characterized by good tolerability: there were no adverse events associated, according to the researcher, with the studied drug.CONCLUSIONS: combined topical product Relief® Pro is effective for hemorrhoids.

Results of a clinical study of the drug efficacy and safety for intravesical administration based on bacteriophages in therapy in patients with chronic recurrent cystitis

Background. Urinary tract infections remain one of the urgent problems in the aspect of qualified medical care. The causative agents of nosocomial infections are becoming more and more resistant to the drugs used, while the rate of new drugs synthesis is lower than the rate of development of antibiotic resistance. Routine and empirical prevention of recurrent urinary tract infections is often ineffective.
 Aim. To study the efficacy and safety of intravesical application of the drug based on bacteriophages in therapy in patients with chronic recurrent cystitis.
 Materials and methods. A clinical study was carried out to study the efficacy and safety of the drug for intravesical administration based on bacteriophages in therapy in patients with chronic recurrent cystitis. The study included 75 patients who were divided into 3 groups in a 1: 1: 1 ratio. In the main group, the drug for intravesical administration based on bacteriophages, as well as rectal suppositories with bacteriophages were used; in the control group only a drug for intravesical administration based on bacteriophages or rectal suppositories with bacteriophages. On visits 1-4, all patients underwent a clinical blood test, general urine analysis, bacteriological urine analysis, as well as urine analysis by the polymerase chain reaction method. The analysis of the patients condition in groups was carried out according to the dynamics of main clinical symptoms changes, data from validated scales for assessing pelvic pain and urgency/frequency of urination and assessment of symptoms of acute cystitis (Acute Cystitis Symptom Score ACSS), as well as the dynamics of changes in objective parameters of laboratory studies and possible changes in sensitivity uropathogens to antibacterial drugs.
 Results. The average age of the patients included in the study was 50.6 years. In all 3 groups, bacteriological examination of urine showed a predominant growth of Escherichia coli (3104 CFU/ml). In the course of the study, there was a good tolerance to therapy, a decrease in clinical symptoms, as well as a significant decrease in the total score according to the pelvic pain scale and urgency/frequency of urination and the ACSS scale in all patients.
 Conclusion. The emergence of a large number of microorganisms resistant to various antibiotics and their rapid spread in the environment has led to an increase in scientific interest in bacteriophage therapy as an alternative method of treatment. The overall subjective effectiveness of the therapy in our study was more than 80%, safety - 100%. Further research will allow for a personalized approach to the treatment of infectious diseases of the urinary system.

Efficacy evaluation of entomological drug Adenoprosin® usage in combined treatment of patients with lower urinary tract symptoms due to benign prostate enlargement

BACKGROUND: Increasing the effectiveness of treatment of patients with symptoms of the lower urinary tract is one of the main problems of modern urology, which is associated both with their high prevalence and with a significant deterioration in the quality of life of patients.
 AIM: The article presents the results of the usage of the entomological drug Adenoprosin in the combined treatment of patients with lower urinary tract symptoms due to benign prostatic enlargement.
 MATERIALS AND METHODS: 80 patients were treated (mean age 63.6 6.4 years). At the initial phase of the study, all patients received Tamsulosin 0.4 mg once a day for 4 weeks. At the second phase, the patients were divided into two groups. Group 1 patients were prescribed a combination therapy with Adenoprosin (1 rectal suppository (150 mg) at night, for a course of 30 suppositories) and Tamsulosin (0.4 mg per day). Patients of the 2nd group continued monotherapy with Tamsulosin (0.4 mg per day). The duration of the second phase of treatment was 4 weeks.
 RESULTS: The results of the study showed a more pronounced positive dynamics of clinical indicators in patients of the 1st group, who received combination therapy with Adenoprosin and Tamsulosin, compared to patients of the 2nd group. There was a more pronounced decrease in the IPSS score, an improvement in the quality of life, an increase in the urine flow rate and a decrease in the volume of residual urine. The volume of the prostate gland did not change significantly. When examined 2 weeks after the end of treatment, the positive dynamics of clinical indicators in patients of the 1st group persisted. The tolerability of the treatment was satisfactory in patients of both groups.
 CONCLUSIONS: The results of the study indicate the advisability of including Adenoprosin in the combination therapy of patients with lower urinary tract symptoms due to benign enlargement of the prostate gland.

The effects of rectal suppositories of Plantago major and Anetheum Graveolens on postpartum hemorrhage: A randomized triple blinded clinical trial

Introductionpostpartum hemorrhage (PPH) is a known emergency in midwifery and is one of the most common causes of maternal mortality. This study sought to investigate the effectiveness of rectal suppositories of Plantago major and Anethum graveolens (Dill) on the PPH. MethodA randomized triple blinded clinical trial was performed on 105 pregnant women who were eligible for the study and admitted to the vaginal delivery unit to Umm-al-Banin Hospital in Mashhad in 2018. Individuals were divided using random assignment into three 35-individual groups, namely Plantago major, Dill, and control groups. Measures were taken according to the hospital routine and participants received an infusion of 30 units of oxytocin after the infant birth. Intervention groups received the first dose of a rectal suppository of Plantago major 120 mg and rectal suppository of dill 290 mg immediately after removal of the placenta and embryonic membranes and uterine massage, and then the next doses were placed every half hour to 5 doses. The PPH was measured by weighing the blood bags and pads 4 h after labor. FindingsAverage bleeding rate at the end of the first 4 h after delivery was 306.2 ± 11.2 cc in the control group, 282.4 ± 9.6 cc in the Dill group, and 253.5 ± 14.2 cc in the Plantago group; there was a statistically significant difference (P = 0.001). ConclusionThe results demonstrated that rectal suppositories of Dill and Plantago are both effective for decreasing PPH, but Plantago rectal suppository can more effectively reduce PPH.

Prophylactic role of ciprofloxacin and ceftriaxone in prostate biopsy-related infection: randomized comparative study of bacterial spectrum and antibiotic sensitivities

BackgroundThe mainstay for the diagnosis of prostate cancer is transrectal ultrasound-guided prostate biopsy. However, prostate biopsy is associated with a significant risk of complications including urinary tract infection. This study aims to compare the bacterial profile and antibiotic susceptibility pattern in urinary tract infection after prostate biopsy between patients on 2 different antimicrobial prophylactic regimens.MethodsThis was a comparative cross-sectional study done at the urology unit of our institution, over 13 months. Fifty-six patients who met the inclusion criteria made up the study population and were randomly assigned to two groups. Those in group 1 (28) received intravenous ciprofloxacin (Juhel) 400 mg at induction of anesthesia, while those in group 2 (28) received intravenous ceftriaxone (Rocephin) 1 g at induction of anesthesia. All patients received bisacodyl (dulcolax) rectal suppositories 20 mg nocte starting 2 nights before the procedure as well as intravenous metronidazole (Juhel) at induction of anesthesia. Urine samples were taken for urine culture and sensitivity three days after biopsy. Isolated organisms and their antibiotics sensitivities were documented. Statistical analysis was done using SPSS version 21.0 with the level of significance set at P < 0.05.ResultsIn group 1 the prevalence of urinary tract infection was 61%. Escherichia coli was isolated in 11(64.71%) cases, Klebsiella species in 3(17.65%), staphylococcus aureus in 1(5.88%), Proteus species in 1(5.88%), and non-hemolytic streptococcus species in 1(5.88%). In this group, all isolated bacterial organisms were resistant to ciprofloxacin. In group 2 the prevalence of urinary tract infection was 43%. Klebsiella spp was isolated in 6(50%) cases, Pseudomonas aeruginosa in 3(25%), E. coli in 2(16.67%), Staphylococcus in 1(8.33%). In group 2 all isolated bacterial organisms were resistant to ceftriaxone.ConclusionCiprofloxacin and ceftriaxone are both associated with a high rate of urinary tract infection when used as prophylaxis for prostate biopsy. The bacterial etiology of prostate biopsy-related urinary tract infection is dependent on the prophylactic antibiotics used. Based on the high rate of urinary tract infection associated with the use of either ciprofloxacin or ceftriaxone, we recommend a combination of both drugs as prophylaxis for prostate biopsy.

Nanostructured lipid carriers based suppository for enhanced rectal absorption of ondansetron: In vitro and in vivo evaluations

The current research aimed to fabricate ondansetron nanostructured lipid carriers (OND-NLCs) and incorporate them into a suppository base to manage chemotherapy-induced vomiting and nausea, which offer the advantage of both rapid onset and prolonged release. NLCs were fabricated by adopting the solvent diffusion method. The binary lipid mixture of oleic acid (liquid lipid) and lauric acid (solid lipid) were prepared in distinct ratios. The NLCs were characterized concerning the surface charge, size, drug encapsulation efficiency, and surface morphology. In addition, the influence of surfactant, co-surfactant, and lipid on entrapment efficiency and particle size was investigated. Phosphate buffer having pH 7.4 is used for evaluating in vitro drug release by utilizing a dialysis membrane. Various kinetics models were used to estimate the drug release kinetics of fabricated nanostructured lipid carriers. The particle size of the NLCs was calculated between 101 and 378 nm with negative zeta potential on the NLC’s surface. The entrapment efficiency was found between 68 and 87%. Scanning Electron Microscopic analysis showed the spherical shape of nanostructured lipid carriers. The dissolution profile of the ondansetron-loaded NLC suppository depicts biphasic behavior of firstly burst release then slow release was observed. The diffusion controlled release was evident from kinetic modeling. The succeeding step comprehended the fabrication and characterization of NLC-based suppositories utilizing NLC formulations that demonstrated the combined advantage of rapid onset, prolonged release, and better in vivo bioavailability as compared to control suppository.

Clinical Pilot Study of Rectal Suppository Containing Combined Extract of Cissus quadrangularis Linn. and Acmella paniculata (Wall ex. DC.) R. K. Jansen in Acute Hemorrhoids.

Background Cissus quadrangularis Linn. (CQ) is a medicinal plant with good evidence for the treatment of hemorrhoids, listed in the Thai National List of Herbal Products in the oral dosage form. Acmella paniculata (Wall ex. DC.) R. K. Jansen. (AP) is a medicinal plant with a local anesthetic effect. Objective To investigate the potential of rectal suppositories containing CQ and AP extracts to alleviate symptoms of hemorrhoids compared with the commercialized rectal suppository containing hydrocortisone and cinchocaine. Materials and Methods Hemorrhoid outpatients (n = 105) with different severity grades (I, II, or III) from eight hospitals in northern Thailand were included in this study. Hemorrhoid severity was graded by proctoscopy associated with either anal pain or bleeding related to hemorrhoids or both. The patients were randomly allocated to two groups: CQ-AP group (n = 52) or the commercialized rectal suppository group (n = 53). One suppository was rectally administered twice daily in the morning and at bedtime for seven days. Evaluations were performed by physicians on days 1, 4, and 8 of the study. The primary endpoints were bleeding and prolapse size, while the secondary endpoint was anal pain. Results Baseline demographics, lifestyle, constipation, number of prolapses, grade of hemorrhoid severity, and duration of experiencing hemorrhoids were comparable in both groups of patients. The effects of CQ-AP and the commercialized rectal suppository on bleeding, prolapse size, and anal pain were comparable. The patients in both groups were satisfied with both products at comparable levels and stated a preference for further use in the case of hemorrhoids recurrence. In terms of safety, the patients in the commercialized rectal suppository group experienced a higher incidence of adverse events, including anal pain and bleeding. Conclusion Rectal suppositories containing a combined extract of CQ and AP show potential in alleviating hemorrhoidal symptoms with a good safety profile.

Comparative study of specific activity of rectal suppositories with clopidogrel

One of the most effective platelet antiaggregants is clopidogrel, inhibiting platelet activation by selectively binding adenosine diphosphate (ADP) with specific receptors. However, in a number of clinical situations it is necessary to have a pronounced antithrombotic effect in the shortest possible time which gives rise to interest in the transmucose use of the drug, in particular, rectal route. The theoretical preconditions for the development of a rectal administration of clopidogrel are based on the data that the anti-aggregation effect of a substance is carried out by its main metabolite formed after “first hepatic passage”, while clopidogrel itself in this aspect is inactive. On the base of complex physico-chemical, pharmaceutical, biopharmaceutical, rheological and microbiological investigations, the rational composition of clopidogrel rectal dosage form – suppository on a hydrophilic base to prevent atherothrombotic events in patients with myocardial infarction, acute coronary syndrome, ischemic stroke, peripheral arterial occlusion, is proposed by the employees of the Department of Technology of Medications of the Zaporizhzhia State Medical University. The aim of the work is to investigate the specific activity of rectal suppositories with clopidogrel. Materials and methods. Experimental suppositories with clopidogrel 0,075 g for rectal administration were used as the objects in pre-line studies. The ability of clopidogrel to reduce the inhibitory effect of ADP on adenylate cyclase activity and decrease the number of binding sites for 2-methylthio-ADP (analogue of ADP) without altering the receptor topography is used as a base of the method of comparative study of its specific activity in the rectal dosage form (suppository) and in comparison with the reference medication Plavix (SANOFI WINTHROP INDUSTRIE, France) in the tablet form. Studies were performed on white non-linear rats of different sexes with different mass 150–210 g, aged 3.5–5.0 months. Results. Statistically significant differences in the inhibition of induced platelet aggregation were registered after 6 hours of rectal administration of clopidogrel and gastric administration of the reference medication, indicating the effectiveness of the rectal applicative transmucosal route for this active pharmaceutical ingredient (API). On the 5th day of administration, inhibition of induced platelet aggregation significantly increased, and that is supported by literature on the cumulative effect of clopidogrel in daily life. When comparing the digital material of the table, it is obvious that the rectal administration of clopidogrel is more effective in comparison with oral route which is probably due to the rapid delivery of API to the liver and the formation of an active metabolite of clopidogrel inhibiting the induction and spontaneous aggregation of platelets in human’s and animal’s blood. Obtained data provide with sound arguments for development of rectal suppositories with clopidogrel because in clinical care faster achievement of an anti-aggregation effect in patients with acute coronary syndrome is the primary task of clinical pharmacology and pharmacy. Conclusions. Using the biochemical model of pathology, it was established that the applicative semisolid medication of clopidogrel in the form of rectal suppository exhibited inductive anti-aggregation activity and its administration didn’t reveal any side effects and undesirable events. Rectal suppositories with clopidogrel have been shown to exhibit faster reliable anti-aggregation effect in comparison with intragastric administration.

Randomized trial of high-dose rectal diclofenac suppository and epinephrine spray on duodenal papilla for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis.

High-dose rectal diclofenac suppository and epinephrine spray on duodenal papilla during endoscopic retrograde cholangiopancreatography (ERCP) may reduce the incidence of post-ERCP pancreatitis. We performed randomized trial to compare the effect of combination of rectal diclofenac and epinephrine spray on papilla (group A) vs. combination of rectal diclofenac with saline spray (group B) for prevention of post-ERCP pancreatitis. We performed a double-blind trial at tertiary care center from April 2018 to May 2020 on 882 patients with naive papilla undergoing ERCP. The patients were randomly assigned togroups, A (n=437) or B (n=445). All patients received a single dose of rectal diclofenac 100 mg within 30 minutes before ERCP; 20 mL of diluted epinephrine 0.02% (group A) or saline (group B) was then sprayed on the duodenal papilla at the end of ERCP. The primary outcome was to compare incidence of post-ERCP pancreatitis (PEP) in two groups. The groups had similar baseline characteristics. PEP developed in 28 patients in group A (6.4%) and 35 patients in group B (7.9%) (relative risk, 1.1; 95% CI, 0.87-1.39; p=0.401). Our study showed that addition of epinephrine spray on duodenal papilla did not reduce the risk of post-ERCP pancreatitis. There is need for further studies to evaluate the role of different concentrations of epinephrine spray on papilla for prevention of post-ERCP pancreatitis. Clinical Trials Registry- India (CTRI/2018/04/013396).

Analysis of the Effectiveness of Various Types of Conservative Therapy for Chronic Bacterial Prostatitis

Analysis of the Effectiveness of Various Types of Conservative Therapy for Chronic Bacterial Prostatitis

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

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

Boswellia resin extract and propolis derived polyphenols in patients with type III chronic prostatitis/chronic pelvic pain syndrome: An Italian prospective multicenter study

ObjectiveTo assess the efficacy and safety of a treatment regimen based on rectal administration of Boswellia resin extract and propolis derived polyphenols in patients with type IIIa and type IIIb chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS). MethodsPatients with type IIIa and type IIIb CP/CPPS received one rectal suppository a day for 15 days per month for 3 consecutive months. Participants were evaluated with National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), the International Prostate Symptom Scores (IPSS), International Index of Erectile Function (IIEF), four-glass test, uroflowmetry, and prostate-specific antigen assessments at baseline and at Week 4, and Week 12. Primary endpoints were improvement in pain domain of NIH-CPSI and improvement of NIH-CPSI total score. Secondary outcomes included improvement of micturition and quality of life (QoL) domains of NIH-CPSI questionnaire. ResultsA total of 61 males were enrolled. No adverse events were reported. Significant improvements from baseline to Day 30 were reported for NIH-CPSI total score (mean difference: −9.2; p<0.01), NIH-CPSI pain domain (mean difference: −5.5; p<0.01), NIH-CPSI micturition domain, NIH-CPSI QoL domain, and IPSS total score (mean difference: −5.6; p<0.01). No significant changes from baseline in terms of IIEF score or maximum flow rate were observed. At final follow-up (Day 90), further significant improvements in terms of NIH-CPSI total score (mean difference: −12.2; p<0.01), NIH-CPSI pain domain (mean difference: −6.6; p<0.01), NIH-CPSI micturition domain, NIH-CPSI QoL domain, and IPSS total score were reported. ConclusionRectal administration of Boswellia resin extract and propolis derived polyphenols is well tolerated and delivers a significant symptomatic improvement in most patients with type IIIa and type IIIb CP/CPPS.

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

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

Effect of Hydrophile-Lipophile Balance (HLB) of Mixed Surfactants on In-Vitro Release Profile of Ibuprofen from Semi-Synthetic Suppository Bases

Background: The emphasis on the use of surfactants in enhancing drug release from fatty suppository bases has always been on the concentration and type of surfactants. However, the Hydrophile-Lipophile Balance (HLB) of the surfactants added can be of significant effect.Objective: The study aimed at evaluating the effect of HLB of the incorporated mixed surfactants on the physical and release properties of Ibuprofen suppositories formulated with semi-synthetic fatty bases.Methodology: The preparations were carried out using 1 g mould. Ibuprofen suppositories, each containing 200 mg of Ibuprofen with semi-synthetic fatty bases (Witepsol® H15, Suppocire® CM), were prepared by fusion method. Mixed surfactants (Span® 80 and Tween® 80) were added at 4 %w/w in varied ratios to give HLB values of 4.3 to 15.0. The physical properties and release profile of the suppositories were evaluated using established procedures.Results: The physical properties of the suppositories met the standard specified in the BP. Addition of mixed surfactants greatly influenced the release of the Ibuprofen from the formulations with optimum release at lipophilic HLB (4.3) and hydrophilic HLB (12.0) for formulations in Suppocire® CM and Witepsol® H15, respectively. The release parameters majorly fitted into Higuchi’s model. The release mechanism was non-Fickian and Fickian for formulations in Suppocire® CM and Witepsol® H15, respectively.Conclusion: The variations observed in the release profiles of Ibuprofen from the suppository bases indicate that HLB value of mixed surfactants can be employed in modifying drug release from semi-synthetic fatty bases