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This review provides a compilation of the methods used to study real-time (37 degrees C) drug release from parenteral microparticulate drug delivery systems administered via the subcutaneous or intramuscular route. Current methods fall into three broad categories, viz., sample and separate, flow-through cell, and dialysis techniques. The principle of the specific method employed along with the advantages and disadvantages are described. With the "sample and separate" technique, drug-loaded microparticles are introduced into a vessel, and release is monitored over time by analysis of supernatant or drug remaining in the microspheres. In the "flow-through cell" technique, media is continuously circulated through a column containing drug-loaded microparticles followed by analysis of the eluent. The "dialysis" method achieves a physical separation of the drug-loaded microparticles from the release media by use of a membrane, which allows for sampling without interference of the microspheres. With all these methods, the setup and sampling techniques seem to influence in vitro release; the results are discussed in detail, and criteria to aid in selection of a method are stated. Attempts to establish in vitro-in vivo correlation for these injectable dosage forms are also discussed. It would be prudent to have an in vitro test method for microparticles that satisfies compendial and regulatory requirements, is user friendly, robust, and reproducible, and can be used for quality-control purposes at real-time and elevated temperatures.

This review summarizes the methods used to study real-time (37 ∘ C) drug release from nanoparticulate drug delivery systems and establish an IVIVC. Since no compendial standards exist, drug release is currently assessed using a variety of methods including sample and separate (SS), continuous flow (CF), dialysis membrane (DM) methods, and a combination thereof, as well as novel techniques like voltametry and turbidimetry. This review describes the principle of each method along with their advantages and disadvantages, including challenges with set-up and sampling. The SS method allows direct measurement of drug release with simple set-up requirements, but sampling is cumbersome. With the CF method, sampling is straightforward but the set-up is time consuming. Set-up as well as sampling is easier with the DM, but it may not be suitable for drugs that bind to the membrane. Novel methods offer the possibility of real-time drug release measurement but may be restricted to certain types of drugs. Of these methods, Level A IVIVCs have been obtained with dialysis, alone or in combination with the sample and separate technique. Future efforts should focus on developing mathematical models that describe drug release mechanisms as well as facilitate formulation development of nano-sized dosage forms.

In humans, the incidence and severity of abdominal aortic aneurysms (AAA) are greater in males than in females. Chronic infusion of angiotensin II (AngII) into apolipoprotein E-deficient (apoE(-/-)) mice promotes atherosclerosis and causes the formation of AAAs. Just as human males are more susceptible to developing AAAs, male mice are more susceptible to AngII-induced AAAs. We hypothesized that sex steroid hormones mediate gender differences in AngII-induced AAA through regulation of the renin-angiotensin system. To define the role of ovarian hormones, female apoE(-/-) mice were subjected to ovariectomy or sham operation and infused with AngII (1000 ng/kg x min) for 28 d. Ovariectomy had no effect on AngII-induced atherosclerosis, nor did it influence the incidence or severity of AAA. To define the role of testicular hormones, male apoE(-/-) mice were subjected to orchidectomy (orx) or sham operation and infused with AngII (1000 ng/kg x min) for 28 d. Orx resulted in a profound reduction in AAA incidence (85% vs. 18%, sham vs. orx; P = 0.003) to the level observed in females (25%). However, orx had no effect on AngII-induced reductions in plasma renin concentration or spleen AngII receptor density. In contrast, orx resulted in an increase in atherosclerosis (0.46 +/- 0.07 vs. 1.20 +/- 0.21 mm(2), sham vs. orx; P = 0.002). These results suggest that estrogen does not mediate gender differences in AngII-induced AAA. In contrast, androgens mediate a higher incidence of AngII- induced AAA, through mechanisms that do not appear to involve circulating renin or angiotensin receptor density.

Background/objective: Reproductive tract infections (RTI) present major health, social, and economic problems in developing countries. Our objective was to describe the prevalence and risk factors of RTIs in a population based sample of women aged 18-45 years. Method: 2494 women of 3000 randomly selected from the population defined by a primary health centre catchment area consented to participate. Participants were interviewed regarding complaints and risk factors. Laboratory specimens were collected for the diagnosis of RTIs. Analyses of risk factors were carried out separately for the outcomes of sexually transmitted infections: chlamydia, gonorrhoea, trichomoniasis; and endogenous infections: bacterial vaginosis (BV) and candida. Results: Endogenous infections were relatively common (BV 17.8%; candida 8.5%), and sexually transmitted infections (STI) were infrequent (4.2%). Factors indicative of poverty and marginalisation were associated with STIs and BV. Gender disadvantage, particularly spousal violence, was associated with BV, while concern about a husband's extramarital relationships, an indicator of sexual risk, was associated with STI. Husband's discharge was strongly associated with STI, and a non-white vaginal discharge was associated with both STI and BV. Condom use and oral contraceptive use were associated with a reduced risk of BV. Conclusions: Most of the population burden of RTIs is attributed to endogenous infections. Socioeconomic deprivation and gender disadvantage are associated with raised risk for BV, while the risk factors for STIs indicated that disadvantaged women were likely to be infected by their husbands.

INTRODUCTION: Endoscopy-related injury (ERI) is common in gastroenterologists (GI). The study aim was to assess the prevalence of self-reported ERI, patterns of injury, and endoscopist knowledge of preventative strategies in a nationally representative sample. METHODS: A 38-item electronic survey was sent to 15,868 American College of Gastroenterology physician members. The survey was completed by 1,698 members and was included in analyses. Descriptive, univariate, and multivariate analyses were conducted to evaluate the likelihood of ERI based on workload parameters and gender. RESULTS: ERI was reported by 75% of respondents. ERI was most common in the thumb (63.3%), neck (59%), hand/finger (56.5%), lower back (52.6%), shoulder (47%), and wrist (45%). There was no significant difference in the prevalence of ERI between men and women GI. However, women GI were significantly more likely to report upper extremity ERI while men were more likely to report lower-back pain-related ERI. Significant gender differences were noted in the reported mechanisms attributed to ERI. Most respondents did not discuss ergonomic strategies in their current practice (63%). ERI was less likely to be reported in GI who took breaks during endoscopy (P = 0.002). DISCUSSION: ERI is highly prevalent in GI physicians. Significant gender differences regarding specific sites affected by ERI and the contributing mechanisms were observed. Results strongly support institution of training in ergonomics for all GI as a strategy to prevent its impact on providers of endoscopy. JOURNAL/ajgast/04.03/00000434-202103000-00021/inline-graphic1/v/2023-07-18T070745Z/r/image-tiff

The purpose of this research was to develop a simple and convenient in vitro release method for biodegradable microspheres using a commercially available dialyzer. A 25 KD MWCO Float-a-Lyzer was used to evaluate peptide diffusion at 37°C and 55°C in different buffers and assess the effect of peptide concentration. In vitro release of Leuprolide from PLGA microspheres, having a 1-month duration of action, was assessed using the dialyzer and compared with the commonly used ''sample and separate'' method with and without agitation. Peptide diffusion through the dialysis membrane was rapid at 37°C and 55°C in all buffers and was independent of peptide concentration. There was no detectable binding to the membrane under the conditions of the study. In vitro release of Leuprolide from PLGA microspheres was tri-phasic and was complete in 28 days with the dialysis technique. With the sample and separate technique, linear release profiles were obtained with complete release occurring under conditions of agitation. Diffusion through the dialysis membrane was sufficiently rapid to qualify the Float-a-Lyzer for an in vitro release system for microparticulate dosage forms. Membrane characteristics render it useful to study drug release under real-time and accelerated conditions.

The purpose of this study was to determine the feasibility of applying accelerated in vitro release testing to correlate or predict long-term in vitro release of leuprolide poly(lactideco-glycolide) microspheres. Peptide release was studied using a dialysis technique at 37°C and at elevated temperatures (50°C-60°C) in 0.1M phosphate buffered saline (PBS) pH 7.4 and 0.1M acetate buffer pH 4.0. The data were analyzed using a modification of the Weibull equation. Peptide release was temperature dependent and complete within 30 days at 37°C and 3 to 5 days at the elevated temperatures. In vitro release profiles at the elevated temperatures correlated well with release at 37°C. The shapes of the release profiles at all temperatures were similar. Using the modified Weibull equation, an increase in temperature was characterized by an increase in the model parameter, α, a scaling factor for the apparent rate constant. Complete release at 37°C was shortened from 30 days to 5 days at 50°C, 3.5 days at 55°C, 2.25 days at 60°C in PBS pH 7.4, and 3 days at 50°C in acetate buffer pH 4.0. Values for the model parameter β indicated that the shape of the release profiles at 55°C in PBS pH 7.4 (2.740) and 50°C in 0.1M acetate buffer pH 4.0 (2.711) were similar to that at 37°C (2.677). The E a for hydration and erosion were determined to be 42.3 and 19.4 kcal/mol, respectively. Polymer degradation was also temperature dependent and had an E a of 31.6 kcal/mol. Short-term in vitro release studies offer the possibility of correlation with long-term release, thereby reducing the time and expense associated with longterm studies. Accelerated release methodology could be useful in the prediction of long-term release from extended release microsphere dosage forms and may serve as a quality control tool for the release of clinical or commercial batches.