Development of Dispersible Vaginal Tablets of Tenofovir Loaded Mucoadhesive Chitosan Microparticles for Anti-HIV Pre-Exposure Prophylaxis.

Tenofovir disoproxil fumarate (TDF)-loaded bioadhesive chitosan microparticles (CM) were developed by an emulsification internal gelation technique. Among different batches produced, ECH-4 was found to display a high % entrapment efficiency (68.93 ± 1.76%) and sustained drug release of 88.05 ± 0.38% at 24 h. Solid state characterization of ECH-4 employing DSC and PXRD indicated that the TDF existed in an amorphous state as a solid-solid solution in chitosan. Scanning electron microscopy revealed CM of ECH-4 was spherical in shape with a rough surface topography. Laser scattering analysis using Malvern Master sizer indicated that particle size of ECH-4 was in the range of 0.52 ± 0.10 µm to 284.79 ± 21.42 µm with a surface-mean diameter of 12.41 ± 0.06 µm. Ex vivo mucoadhesion studies using rabbit mucosa as a substrate indicated that 10.34 ± 2.08% of CM of ECH-4 was retained at the end of 24 h. The microparticles of ECH-4 were incorporated into dispersible tablets (DT-TCM) intended for intravaginal administration, in view to arrest the pre-exposure transmission of HIV during sexual intercourse. In vitro release from the dispersible tablet (F3) into simulated vaginal fluid (pH 4.5) displayed a sustained release profile of TDF as 89.98 ± 1.61% of TDF was released at 24 h. The in vitro dissolution profile of the DT-TCM was found to be similar to that of TDF loaded CM with the values of f1 (difference factor) and f2 (similarity factor) being 1.52 and 78.02, respectively. Therefore, DT-TCM would be a promising novel drug delivery platform for pre-exposure prophylaxis against HIV.

Comparison of fetal safety of vaginal Misoprostol tablet and Dinoprostone gel for induction of labor: An open-label randomized control trial.

AIM: In modern obstetrics, need of labor induction is increasing along with increased caesarean deliveries. Major contributions for these operative deliveries are due to induction failure. This demands a potent labor-inducing agent. Dinoprostone gel is an established method but having some drawbacks. Misoprostol could be an effective alternative to Dinoprostone, but its fetal safety is not yet well established. This study aimed to evaluate the fetal safety of vaginal Misoprostol tablet by measuring fetal heart rate changes during induction of labor. METHODS: This was a single-center randomized controlled trial incorporating 140 term women, equally randomized to get either tablet Misoprostol or Dinoprostone gel. Fetal heart rate patterns were compared in both the groups by continuous cardiotocographic tracing. All the data were analyzed on an intention-to-treat basis. RESULTS: There were no statistically significant changes in fetal heart rate pattern in both Misoprostol and Dinoprostone groups. Vaginal deliveries were statistically higher in Misoprostol group. Neonatal parameters like 1 min Appearance, Pulse, Grimace, Activity, and Respiration score and neonatal intensive care unit admission were comparable, and there was no significant difference in terms of major adverse events and side effects. CONCLUSIONS: Misoprostol is a safe alternative to Dinoprostone gel for induction of labor and found to be more effective labor-inducing agent. In the background of higher caesarean rate, vaginal Misoprostol can be a potential labor-inducing agent especially in a resource poor setting.

Multiple use applicator for vaginal tablets/vaginal inserts: compliance verification and suitability studies.

BACKGROUND: A newly developed multiple use applicator for vaginal tablets/vaginal inserts* was evaluated for its general suitability. There are no standard procedures described in guidelines or general accepted publications as to how this kind of product should be tested for suitability of purpose. METHODS: Due to the lack of existing standard procedures, three separate tests were designed and successful executed: (a) First, a patient acceptability evaluation was carried out as part of a phase III trial (registered in EudraCT on 9 Jan 2017, number 2017-000142-22 2. https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number%3A2017-000142-22 ). (b) Secondly, a cleaning procedure for the applicator after simulated multiple use was developed and verified in order to prove a minimized risk of microbiological contamination of the device. A newly developed vaginal fluid to simulate multiple applications was applied for this trial. (c) Lastly, a third trial evaluated the mechanical stability and proper functionality of the applicator after multiple simulated uses. Even potential abrasion of material of the device was checked. RESULTS: Acceptable patient compliance of the new multiple use applicator was verified after 2 weeks of daily use. Furthermore, diary data assessments of patients participating in the Pharmacodynamic part of the trial were evaluated as well. Overall, patient acceptability of the new applicator was proven. The easy-to-use cleaning procedure for the applicator, which can even be carried out in a domestic environment, was developed and successfully verified for effectiveness, meeting all microbiological acceptance criteria for vaginal products of the European Pharmacopeia. The mechanical stability and proper functionality of the applicator after 50 simulated uses was also evaluated. All tested applicator batches (fresh and aged) passed the final evaluation, with no limitations in functionality. CONCLUSION: The tests developed and executed consider various compliance aspects of the newly developed applicator. Results of these individual tests met the expectations and/or the predefined acceptance criteria. All included trials performed produced results justifying and qualifying the applicator for the intended multiple-use. The procedures outlined may also be a guide as to how this kind of medical device can be tested for suitability. Trial registration Registered in EudraCT, number 2017-000142-22, start date 24 May 2017.

Preventive effect of metronidazole vaginal tablets on vaginal bacteria-related postoperative complications with total laparoscopic hysterectomy.

BACKGROUND: The use of total laparoscopic hysterectomy is increasing. However, as with conventional abdominal hysterectomy, vaginal bacteria-related postoperative complications need to be managed in total laparoscopic hysterectomy. Therefore, we started to combine metronidazole vaginal tablets with intravenous administration of cephem antibiotics immediately before starting surgery to reduce complications. To evaluate the effect of this combination, and to determine the risk factors for these complications, we retrospectively collected medical records from our hospital and performed a multivariate analysis. METHODS: We reviewed the medical records of 520 patients who underwent total laparoscopic hysterectomy from 1 January 2015 to 31 December 2021. Among these cases, we identified 16 cases as having vaginal bacteria-related postoperative complications, defined as needing more than one additional day for treatment of postoperative complications, namely postoperative infection (10 cases) and vaginal dehiscence (6 cases). First, we evaluate the effect of metronidazole vaginal tablets by dividing the patients into two groups according to whether metronidazole vaginal tablets were used, and comparing the vaginal bacteria-related postoperative complication rates and other indices. Second, we performed a multivariate logistic regression analysis to assess the influence of each of 17 representative factors, including patient characteristics and symptoms, uterus and leiomyoma sizes, concomitant procedures such as laparoscopic cystectomy and pelvic lymphadenectomy, and others. RESULTS: In the multivariate analysis of the 520 cases, we confirmed that the use of metronidazole vaginal tablets could reduce the vaginal bacteria-related postoperative complications rate by more than half (odds ratio, 0.36). In addition to metronidazole vaginal tablets use, concomitant laparoscopic cystectomy and blood transfusion were associated with significant increases in the vaginal bacteria-related postoperative complication rate. CONCLUSIONS: The effect of the addition of metronidazole vaginal tablets to pre- and postsurgical treatment on the reduction of vaginal bacteria-related postoperative complications was confirmed. This easy, safe, and low-cost method may improve the management of total laparoscopic hysterectomy.

A Randomised Controlled Trial Comparing Induction of Labour with the Propess Vaginal System to the Prostin Vaginal Tablet in Premature Rupture of Membranes at Term.

Aim: To compare the perinatal outcome and delivery intervals after the induction of labour with the Prostin vaginal tablet versus the Propess vaginal system in pregnant women with term-PROM. Design: One centre paralleled randomised controlled trial with a computer-generated table to allocate treatments. Setting: University Medical Centre in Slovenia. Participants: A total of 205 singleton healthy pregnant women with term-PROM. Intervention: Induction of labour with the Propess vaginal system (intervention group) versus Prostin tablets (control group). Main outcomes: The rate of failed inductions, complications in labour, time intervals between the PROM, induction, the beginning of the active phase, and delivery. Results: A total of 104 patients received Prostin, and 101 patients received Propess. Induction failure rates in the Prostin and the Propess groups were 8/104 (7.7%) and 5/101 (5.0%), respectively (p = 0.80). Delivery abnormalities were uncommon and comparable across the groups. The rates of caesarean sections in the Prostin and Propess groups were 4/96 (4.2%) and 6/96 (6.3%), respectively. The delivery intervals were comparable across the groups. Conclusions: In term-PROM pregnancies, the Propess vaginal system is a safe and effective option for inducing labour.

Combined vaginal administration of nystatin, diiodohydroxyquin, and benzalkonium chloride versus oral metronidazole for the treatment of bacterial vaginosis.

OBJECTIVE: To compare combined vaginal administration of nystatin, diiodohydroxyquin, and benzalkonium chloride versus oral metronidazole for the treatment of bacterial vaginosis (BV). METHODS: A randomized controlled trial was conducted among women diagnosed with BV using the Amsel criteria (n=90) at a university hospital in Khon Kaen, Thailand, between June 27, 2017, and April 30, 2018. The oral metronidazole group (n=44) received 400 mg of metronidazole, administered three times per day. The combined vaginal tablet group (n=46) received a vaginal suppository once daily, which comprised nystatin (100 000 U), diiodohydroxyquin (100 mg), and benzalkonium chloride (7 mg). Treatment was administered for 7 days in both groups. Follow-up visits at 14 and 42 days assessed treatment outcomes and adverse effects. RESULTS: Remission of BV occurred among 41 (93%) women in the oral metronidazole group and 39 (85%) women in the combined vaginal tablet group. The adjusted relative risk was 0.92 (95% confidence interval 0.80-1.06). The rate of nausea and/or vomiting was significantly higher in the oral metronidazole group than that in the combined vaginal tablet group. CONCLUSION: Treatment efficacy of the combined vaginal tablet versus oral metronidazole was equivalent. CLINICAL TRIAL REGISTRATION: TCTR20170627001 (www.clinicaltrials.in.th).

17-α Hydroxyprogesterone Nanoemulsifying Preconcentrate-Loaded Vaginal Tablet: A Novel Non-Invasive Approach for the Prevention of Preterm Birth.

Preterm birth (PTB) is a major cause of infant mortality in the United States and around the globe. Makena®-once-a-week intramuscular injection of 17-α Hydroxyprogesterone caproate (17P)-is the only FDA approved treatment for the prevention of PTB. Invasive delivery of 17P requires hospitalization and expert personnel for injection. Vaginal delivery of 17P would be preferable, because of high patient compliance, reduced systemic exposure, fewer side effects, and no need for hospitalization. The objective of the present study was to prepare and evaluate a self-nanoemulsifying vaginal tablet of 17P. A solid self-nanoemulsifying preconcentrate (S-SNEDDS) of 17P and dimethylacetamide (DMA) was developed using medium chain triglycerides, a non- immunogenic surfactant, and co-processed excipient (PVA-F100). The tablet prepared was characterized for emulsification time, particle size, solid state properties, and drug release. The formulation showed >50% inhibition of TNF-α release from LPS-stimulated RAW 264.7 cells. Importantly, there were significant differences in rates of PTB and average time to delivery between control and vaginal 17P-treated groups in LPS-stimulated timed pregnant E15.5 mice. Considering the lacuna of therapeutic approaches in this area, vaginal delivery of 17P for the prevention of preterm birth has significant clinical relevance.

A novel double-layer mucoadhesive tablet containing probiotic strain for vaginal administration: Design, development and technological evaluation.

Vulvovaginal candidosis caused by Candida spp. is the most prevalent vaginal infection in Europe and the second one in EE.UU, so it has become a major female concern. Probiotics bacteria have been proposed as an alternative treatment with the aim of avoiding the adverse effects associated with conventional therapies including antibiotics and other aggressive drugs for the vaginal mucosa and microbiota. The purpose of this work was to design and develop a novel vaginal tablet that contained Lactobacillus spp. bacteria as a treatment against vulvovaginal infections. A total of 21 two-layers vaginal tablets, which contained different polymeric ratios, were proposed. However, formulation F4 (20mg Na-CMC; 50mg Carbopol® 934; 20mg chitosan) was selected as optimal according to its swelling index and dissolution/erosion capability. F4 tablets showed suitable technological properties for vaginal administration as well as mucoadhesion time (24.36±0.88h) and force (0.0941N). Disintegration assay in simulated vaginal fluid (SVF, pH5.5) showed that effervescent layer disappeared in 27.48±0.05s whilst matrix layer was totally gelled in 1h. Two different release profiles were achieved; on the one hand, a promptly release due to the dissolution of both effervescent layer and matrix layer's surface (1.10×108CFU/g), on the second hand, a prolonged released of the remaining bacteria until 24h (5.48×107CFU/g). For stability and storage study, it was found that bacteria viability was constant until 90days in both ways of storage, in a desiccator and at room temperature, with a final dosage of 108CFU/g which was considered appropriate for vaginal therapy (108-1010CFU/g).

The effects of the thiolation with thioglycolic acid and l-cysteine on the mucoadhesion properties of the starch-graft-poly(acrylic acid).

The aim of this study is to investigate the effects of the thiolation on the mucoadhesion characteristics of the gelatinized and crosslinked wheat starch-graft-poly(acrylic acid) [(WS-g-PAA)gc] for potential use in drug delivery via vaginal route. Thiolation of (WS-g-PAA)gc was first time realized using l-cysteine hydrochloride monohydrate (CyS) and thioglycolic acid (TGA). These conjugates [(WS-g-PAA)gcth] were characterized using FTIR. The free SH group, mucoadhesion, cytotoxicity characteristics and the mechanism of the thiolation were also evaluated. To obtain fundamental data for possible application such as drug carrier, in vitro and in vivo progesterone release profiles from the mucoadhesive tablet formulations were also determined. The results showed that, vaginal tablet containing (WS-g-PAA)gc-TGA, which has not contain free SH groups in its structure, displays higher mucoadhesion than (WS-g-PAA)gc and (WS-g-PAA)gc-CyS. This tablet formulation can also be used as a drug carrier in vaginal applications.

Disulfiram-loaded immediate and extended release vaginal tablets for the localised treatment of cervical cancer.

OBJECTIVES: To develop and manufacture both immediate and sustained release vaginal tablets containing the anticancer drug disulfiram, which has the potential to be used as a non-invasive treatment for cervical cancer. METHODS: Disulfiram-loaded vaginal tablets were manufactured at pilot scale using the direct compression method. These tablets were tested in accordance with the European Pharmacopeia testing of solid dosage form guidelines. They were also tested using a biorelevant dissolution method as well as a dual-chambered release model designed to better mimic the dynamic nature of the vaginal vault. KEY FINDINGS: We have developed both immediate and sustained release vaginal tablets, which when manufactured at pilot scale are within the limits set by the European Pharmacopeia for the testing of solid dosage forms. Furthermore, these tablets are capable of releasing disulfiram in vitro using the dual-chambered release model at levels 25,000 times and 35,000 times greater than its IC50 concentration for the HeLa cervical cancer cell line. CONCLUSIONS: The successful pilot manufacture and testing of both the immediate and sustained release disulfiram-loaded vaginal tablets warrant further investigation, using an in-vivo model, to assess their potential for use as a non-invasive treatment option for cervical cancer.

Conception control by vaginal administration of pills containing ethinyl estradiol and dl-norgestrel.

One hundred twenty-four women of reproductive age have used vaginal pills containing 50 micrograms dl-norgestrel and 35 micrograms ethinyl estradiol to prevent conception for periods ranging from 6 to 20 months. One thousand four hundred thirty-eight woman-months were recorded. No pregnancies occurred. Cycle control was good. Bleeding usually lasted 3 to 5 days, and the interval between withdrawal bleeding events was 26 to 30 days in 86% of the cycles. Amenorrhea, breakthrough bleeding, and spotting occurred rarely. The continuation rate at 1 year was 64%.

PIP: This paper reports the results of a clinical trial of124 women of reproductive age who relied on daily administration of a vaginal pill containing 50 mg dl-norgestrel in combination with 35 mcg ethinyl estradiol fro contraceptive purposes for 6-20 months. No pregnancies occurred in 1438 woman-months of abservation. Bleeding generally developed 3-5 days after insertion of the last pill and lasted an average of 3-5 days. The interval between withdrawal bleeding events was 26-30 days in 86% of cycles. Incidence of intermenstrual bleeding, spotting, and amenorrhea was minimal. No siginificant alterations in blood pressure or blood cell counts and hematocrit were noted. Vaginal discharge requiring treatment developed in 20.9% od subjects; however, this incidence is comparable to that found in oral contraceptive (OC) and IUD users and may thus be unrelated to the vaginal pill. After 1 year of use, 64% of the subjects opted to continue the vaginal pill. This contrasts favorably with continuation rates recorded at the same clinic for vaginal ring users (48%) and OC users (47%). Only 7 of the 44 vaginal pill discontinuers cited medical reasons; the majority gave trivial reasons, and several reapplied for inclusion in the vaginal pill trial a few months after discontinuation. These findings suggest that the vaginal pill avoids the undesirable side affects of the vaginal ring (e.g., expulsion, interference with coitus, odor) as well as those associated with the gastric absorption os steroids, demonstrates a low incidence of complications, and is highly effective in preventing pregnancy.

Ovulation suppression in women following vaginal administration of oral contraceptive tablets.

PIP: A preliminary trial was conducted to test the possibility of using intravaginally a contraceptive tablet manufactured for oral use to achieve ovulation suppression. 12 women who could not continue with oral contraceptives (OCs) because of gastrointestinal complaints and/or nausea volunteered to participate. All subjects discontinued oral use of tablets for at least 2 months prior to the vaginal administration. Condoms were provided for use during the interim period. Patients were instructed to manually place in the vagina either 1 (4 subjects) or 2 tablets (8 subjects) daily for 21 days. Progesterone blood levels remained at preovulatory levels, below 2 ng/ml, throughout the treatment period, indicating that ovulation was suppressed in all subjects. Levels of 17beta-estradiol (32) which showed considerable variation during the control cycle remained low during the treatment cycle. Withdrawal bleeding occurred 2-5 days following the last tablet and lasted 3-5 days, as in normal menstruation. In patients inserting 1 tablet, intermenstrual spotting was common, but in those inserting 2 tablets daily no spotting occurred. 5 of 6 subjects who complained of nausea during OC use reported no nausea during the period of vaginal administration. These patients requested vaginal administration as a regular contraceptive method.^ieng

Clinical use of oral contraceptives administered vaginally: a case report.

PIP: Effectiveness in cycle control and plasma steroid levels were monitored in a woman with promyelocytic leukemia being treated with chemotherapy, given 2 combined oral contraceptives given vaginally. The 18-year old woman had been taking an oral contraceptive containing 50 mcg mestranol and 1 mg norethindrone during the 3 months since she began treatment for leukemia. After recurrence of leukemia, she developed acute hemorrhagic mucocitis and inability to swallow while on cytosine arabinoside, daunorubicin and etoposide. She was administered 2 of the same oral contraceptives daily per vagina, and her withdrawal bleeding continued to be suppressed for 6 weeks while receiving transfusions for aplastic marrow. Compared to 10 normal women taking 30 mcg ethinyl estradiol and 100 mcg norethindrone, the patient's plasma level of radioimmunoassayed ethinyl estradiol was comparable as to concentration and peak time. Her level of norethindrone was lower, with the highest level measured at 12 hours, compared to a peak at 2 hours in women taking one pill orally.^ieng

A clinical trial of Neo Sampoon vaginal contraceptive tablets.

Results are reported of a clinical trial of Neo Sampoon vaginal contraceptive tablets, conducted by the International Fertility Research Program (IFRP) in collaboration with the Dacca Medical College Hospital, Bangladesh. Of the 150 women enrolled, 115 remained in the study at the end of 12 months. The 12-month cumulative gross life-table rates per 100 women were 6.5 for pregnancy and 24.8 for discontinuation due to other reasons. Discomfort associated with the heart generated by the tablets' effervescence was the primary side effect of Neo Sampoon use, and was one of the major causes of discontinuation. Regularity of use and acceptability of this foaming tablet appeared to be high compared to other barrier methods. Further research is needed on Neo Sampoon and other vaginal contraceptives to develop and promote methods that can help meet the worldwide demand for fertility control.

PIP: In mid-1978, the International Fertility Research Program initiated a clinical trial of Neo Sampoon Loop vaginal tablet contraceptives. Data were recorded on standardized forms in several countries. The Bangladesh study was conducted at the Dacca Medical College Hospital. Results from the Bangladesh study are discussed and tabulated. The study showed good acceptability of this method. Of the 150 women enrolled in the study, 115 were still in it after 12 months. After 12 months, there was a 6.5/100 women pregnancy rate and a 24.8/100 women discontinuation rate. These rates are encouraging since most of the women had no previous experience with barrier contraception. Discomfort and a burning sensation were the main reasons for discontinuance. This method can be easily distributed outside the medical system, a system which will be necessary if all at-risk people in the world are to be covered. The fact that regularity of use fell off by 12 months indicates that sustaining motivation may be the main problem with this method of contraception.

A clinical trial of Neo Sampoon vaginal tablets and Emko foam in Alexandria, Egypt.

Results are reported for a comparative 12-month study of Neo Sampoon foaming vaginal tablets containing 60 mg of the spermicide, menfegol, and Emko vaginal foam containing an 8.0% concentration of the spermicide, nonoxynol-9. Conducted in cooperation with the Family Planning Association in Alexandria, Egypt, the trial included 349 women who were randomly allocated to use one of the two contraceptive products. The twelve-month cumulative life-table rate for accidental pregnancy (per 100 women) was 2.8 for Neo Sampoon tablet users and 2.1 for Emko foam users. The 12-month continuation rates were 77.6 and 77.2 per 100 women for the tablet and foam groups, respectively. In both groups, the majority of discontinuations from the study were for personal reasons, including lack of confidence in the method, messiness, partner's objection and a burning sensation. Few women reported a product-related complaint while using their assigned contraceptive method. The most commonly reported complaint for both methods was that use of the product led to an uncomfortable burning sensation for the woman and/or her partner. This complaint, however, was cited by less than 5% of the women in each group. Thus, a combination of low pregnancy rates, few complications and complaints and high continuation rates confirm the relative acceptability, effectiveness and short-term safety of these methods of contraception among this sample of Egyptian women.

PIP: Results are reported for a 12-month study of Neo Sampoon foaming vaginal tablets containing 60mg of the spermicide, menfegol, and EMKO vaginal foam containing an 8.0% concentration of the spermicide, nonoxynol-9. Conducted in cooperation with the Family Planning Association in Alexandria, Egypt, the trial included 349 women randomly allocated to use 1 of 2 contraceptive products. The 12-month cumulative life-table rate for accidental pregnancy (per 100 women) was 2.8 for Neo Sampoon tablet users and 2.1 for Emko foam users. The 12-month continuation rates were 77.6 and 77.2/100 women for the tablet and foam groups, respectively. In both the majority of discontinuations from the study were for personal reasons, including lack of confidence in the method, messiness, partner's objection and a burning sensation. Few women reported a product-related complaint while using their assigned contraceptive method. The most commonly reported complaint for both methods was that use of the product led to an uncomfortable burning sensation for the woman and/or her partner. This complaint, however, was cited by 5% of the women in each group. Thus, a combination of low pregnancy rates, few complications and complaints and high continuation rates confirm the relative acceptability, effectiveness and short-term safety of these methods of contraception among this sample of Egyptian women.

Clinical acceptability, use-patterns and use-effectiveness of the vaginal contraceptive sponge and Neo Sampoon tablets--an international multi-center randomized clinical trial.

This paper describes the results from a randomized clinical trial comparing the Collatex vaginal contraceptive sponge (a predecessor of the Today sponge) and Neo Sampoon foaming vaginal contraceptive tablets; the trial was conducted from 1979 to 1983 in four centers located in three countries (two in Yugoslavia and one each in Taiwan and Bangladesh). The sponge was associated with more insertion and retention problems than the tablet, especially in the two Asian centers. More Neo Sampoon users complained of a burning or stinging sensation. This complaint, however, seemed to be well-tolerated and was not a frequent reason for irregular use and/or discontinuation of use of the tablets. Clinically significant medical complications were rarely reported for either method. Sponge users were more likely to report irregular use than tablet users, primarily due to inconvenience of use. Rates of discontinuation at six months of use were also consistently higher among sponge users than Neo Sampoon users in the four centers. Life-table pregnancy rates at 12 months of use ranged from 3.8 to 18.2 per 100 sponge users and 6.2 to 29.9 per 100 Neo Sampoon users, based on data from the two Yugoslavian centers and the Taiwan center (data from the Bangladesh center were excluded from analysis of pregnancy rates). Practical implications of these findings are discussed.

PIP: This paper describes the results from a randomized clinical trial comparing the Collatex vaginal contraceptive sponge (a predecessor of the Today sponge) and Neo Sampoon foaming vaginal contraceptive tablets; the trial was conducted from 1979 to 1983 in 4 centers located in 3 countries (2 in Yugoslavia and 1 each in Taiwan and Bangladesh). The sponge was associated with more insertion and retention problems than the tablet, especially in the 2 Asian centers. More Neo Sampoon users complained of a burning or stinging sensation. This complaint, however, seemed to be well-tolerated and was not a frequent reason for irregular use and/or discontinuation of use of the tablets. Clinically significant medical complications were rarely reported for either method. Sponge users were more likely to report irregular use than tablet users, primarily due to inconvenience of use. Rates of discontinuation at 6 months of use were also consistently higher among sponge users than Neo Sampoon users in the 4 centers. Life-table pregnancy rates at 12 months of use ranged from 3.8 to 18.2/100 sponge users and 6.2 to 29.9/100 Neo Sampoon users, based on data from the 2 Yugoslavian centers and the Taiwan center (data from the Bangladesh center were excluded from analysis of pregnancy rates). Practical implications of these findings are discussed.

A comparative study of Neo Sampoon, Ortho Vaginal Tablets and Emko Vaginal Tablets in Accra, Ghana.

Neo Sampoon is an effervescent contraceptive vaginal tablet manufactured in Japan that contains 60 mg of the spermicide menfegol. Ortho Vaginal Tablets (OVT) and Emko Vaginal Tablets (EVT), both containing 100 mg of the spermicide nonoxynol-9, were manufactured in the USA. The three products were compared in a randomized clinical trial conducted at the family planning clinics of the Korle-Bu Teaching Hospital and the Kotobaabi Polyclinic in Accra, Ghana. Three-hundred volunteers participated. At 12 months, the life-table pregnancy rates were 9.6, 11.3 and 12.5 per 100 women in the Neo Sampoon, OVT and EVT groups, respectively (p greater than 0.10). More EVT than Neo Sampoon or OVT users discontinued because of discomfort as well as for other product-related reasons (p less than 0.01). The most common reason for discontinuation was the temporary absence of sexual partner, with more than 40% of the women overall terminating for this reason. The 12-month life-table continuation rates per 100 women were higher for the Neo Sampoon group (62.4) than the OVT group (48.6) or the EVT group (38.5) (p less than 0.01). The effectiveness of the three products seems to be similar, but Neo Sampoon and OVT appear to be more acceptable than EVT in this Ghanaian population.

PIP: The effectiveness and acceptability of 3 vaginal tablets (VTs)--Neo Sampoon, Ortho (OVT) and Emko (EVT)--were compared in a clinical trial conducted at the family planning clinics of Korle-Bu Teaching Hospital and Kotobaabi Polyclinic in Accra, Ghana. Subjects included 300 sexually active women ages 18-40 years who were randomly allocated to 1 of the 3 contraceptive methods. The results suggest that, although the effectiveness of the 3 tablets is comparable, Neo Sampoon and OVT are more acceptable than EVT. EVT acceptors reported poorer product compliance, more method-related complaints, and a higher rate of discontinuation. The proportion of women reporting 1 or more method-related complaints (e.g., burning or stinging) during the 1-year study period was 8.9% among Neo Sampoon acceptors, 11.5% among women in the OVT group, and 32.6% among subjects in the EVT group. However, the prevalence of these complaints, and that of increased vaginal discharge, diminished with time in all 3 study groups. Within 12 months, there had been 33 discontinuations in the Neo Sampoon group, 47 among OVT acceptors, and 57 in the EVT group. Over 40% of these discontinuations were a result of temporary absence of the sexual partner, and another 19% reflected non-method-related reasons such as desiring a pregnancy. On the other hand, discontinuation for discomfort or product-related reasons was significantly higher among EVT acceptors compared to Neo Sampoon and OVT acceptors. There were 7 unplanned pregnancies in the Neo Sampoon group (12 month cumulative pregnancy rate 9.6/100), 8 in OVT group (11.3/100), and 9 among EVT acceptors (12.5/100). 9 (38%) of the 24 pregnancies occurred in the 1st month of tablet use and only 1 pregnancy occurred 6 months or more after admission, suggesting that lack of familiarity contributed to method failure. 12-month continuation rates were significantly higher among Neo Sampoon acceptors (62.4/100) than among OVT (48.6/100) or EVT (38.5/100) acceptors.

Ovulation inhibition following vaginal administration of pills containing norethindrone and mestranol.

Plasma levels of estradiol and progesterone were investigated in women using daily vaginal pills containing 1 mg norethindrone and 50 mcg mestranol. Of 13 treatment cycles in ten women using one vaginal pill daily, six were ovulatory and seven anovulatory. All 12 cycles in ten women using two vaginal pills daily were anovulatory.

PIP: Plasma levels of estradiol and progesterone were investigated in 20 healthy women, 21-28 years of age, using daily vaginal pills containing 1 mg norethindrone and 50 mcg mestranol. All patients were using a copper T IUD for 1 year or longer. Blood samples were provided 2-3 times a week during a control pretreatment cycle and during 1 or more treatment cycles. Plasma estradiol and progesterone were measured by radioimmunoassay. Each of 2 groups of 10 women was instructed to insert either 1 or 2 pills daily for 21 days in the vagina, always at the same time of day. A total of 25 treatment cycles was available for analysis. Of the 10 women inserting 1 pill daily, 13 treatment cycles were available. In 6 of these cycles, both progesterone and estradiol levels remained within the normal ovulatory pattern, indicating that ovulation occurred. In the remaining 7 cycles, no preovulatory estrogen peak nor postovulatory progesterone rise occurred, indicating that no ovulation occurred. Of the 10 women inserting 2 pills daily, 12 cycles were available for analysis. In all 12 cycles, no rise in progesterone levels occurred, indicating that ovulation was suppressed. In some cycles estradiol levels rose above 300 pg/ml but progesterone levels remained below 2 ng/ml. Except for 1 patient who complained of vaginal irritation with pruritus, no side effects associated with vaginal pill insertion occurred. In a previous study it was shown that a combination pill containing dl-norgestrel and ethynylestradiol could inhibit ovulation. This studies shows that another combined pill containing norethindrone and mestranol may be as effective as the norgestrel ethynylestradiol combination. To obtain contraceptive efficacy, 2 mg of norethindrone and 100 mcg of mestranol have to be administered daily. The requirement for higher dose by the vaginal route as compared to the oral route stems from the fact that much lower blood levels of the steroids are obtained through vaginal absorption. This dose could be contained in a single tablet if the compounds tested in this study are to be used as a vaginal pill contraceptive.

[Comparative clinical study of 5 barrier methods]. / Estudio clínico comparativo de cinco métodos de barrera.

PIP: The effectiveness and acceptability of 5 barrier methods of contraception were investigated in 171 males and 407 women. They chose the use of ovules with 0.4 mg phenylmercuric acetate; foaming tablets with mephengol; 60 mg ovules with nonoxynol 9, 5.8%; and polymeric sponges with nonoxynol 9 at different concentrations. Anticonceptive effectiveness was evaluated by the Pearl's Index; the lowest rating (6.0) was for the preservative. In decreasing order came mephengol tablets (33.4), phenylmercuric ovules (33.0), nonoxynol ovules (60.7), and polymeric sponges (52.8-120.0). In general the acceptability was low. Discontinuation of spermaticides was due to unreliability; dissatisfaction was the reason for discontinuation of the preservatives and sponges. There were no important side effects. Some couples using foaming tablets reported a sensation of heat as the tablet was dissolving and 2 users reported a bad vaginal odor. After favorable initial acceptance of these methods, final acceptance was low, possibly due to the association with intercourse and direct manipulation of the genitals. (author's)^ieng

[Current role of other contraceptive methods]. / La place actuelle des autres méthodes contraceptives.

PIP: Oral contraception and the use of an IUD are not well accepted by all those who want contraception, mainly because of the many undesirable side effects. There are other contraceptive methods which can still be highly effective while being safe and totally reversible. The Ogino-Knaus method, or rhythm, or calendar method is very effective especially if used in conjunction with the temperature method. It does imply sexual abstinence for a few days every month, correct information on the method itself, and a very regular menstrual cycle; as such it cannot be accepted by everybody, The condom, when properly used, is highly effective, safe, and helps prevent venereal diseases. The use of a vaginal diaphragm implies a little manual dexerity on the part of the woman, and must be used with a spermicidal agent. Spermicidal contraceptive agents include a vast array of creams, foams, jellies, tablets, and, these days, even sponges. They are effective, but require an unpleasant interruption of the sexual act. When no contraceptive method is available at least coitus interruptus must be practiced, followed by vaginal ablutions.^ieng