Effectivity of advanced wastewater treatment: reduction of in vitro endocrine activity and mutagenicity but not of in vivo reproductive toxicity

Abstract

Conventional wastewater treatment plants (WWTPs) have a limited capacity to eliminate micropollutants. One option to improve this is tertiary treatment. Accordingly, the WWTP Eriskirch at the German river Schussen has been upgraded with different combinations of ozonation, sand, and granulated activated carbon filtration. In this study, the removal of endocrine and genotoxic effects in vitro and reproductive toxicity in vivo was assessed in a 2-year long-term monitoring. All experiments were performed with aqueous and solid-phase extracted water samples. Untreated wastewater affected several endocrine endpoints in reporter gene assays. The conventional treatment removed the estrogenic and androgenic activity by 77 and 95 %, respectively. Nevertheless, high anti-estrogenic activities and reproductive toxicity persisted. All advanced treatment technologies further reduced the estrogenic activities by additional 69–86 % compared to conventional treatment, resulting in a complete removal of up to 97 %. In the Ames assay, we detected an ozone-induced mutagenicity, which was removed by subsequent filtration. This demonstrates that a post treatment to ozonation is needed to minimize toxic oxidative transformation products. In the reproduction test with the mudsnail Potamopyrgus antipodarum, a decreased number of embryos was observed for all wastewater samples. This indicates that reproductive toxicants were eliminated by neither the conventional nor the advanced treatment. Furthermore, aqueous samples showed higher anti-estrogenic and reproductive toxicity than extracted samples, indicating that the causative compounds are not extractable or were lost during extraction. This underlines the importance of the adequate handling of wastewater samples. Taken together, this study demonstrates that combinations of multiple advanced technologies reduce endocrine effects in vitro. However, they did not remove in vitro anti-estrogenicity and in vivo reproductive toxicity. This implies that a further optimization of advanced wastewater treatment is needed that goes beyond combining available technologies.

http://ift.tt/2c9O9x1

The Rest of the Story: A Qualitative Study of Complementing Standardized Assessment Data with Informal Interviews with Older Patients and Families

Abstract

Background

While standardized health assessments capture valuable information on patients' demographic and diagnostic characteristics, health conditions, and physical and mental functioning, they may not capture information of most relevance to individual patients and their families. Given that patients and their informal caregivers are the experts on that patient's unique context, it is important to ensure they are able to convey all relevant personal information to formal healthcare providers so that high-quality, patient-centered care may be delivered. This study aims to identify information that older patients and families consider important but that might not be included in standardized assessments.

Methods

Transcripts were analyzed from 29 interviews relating to eight patients with hip fractures from three sites (large urban, smaller urban, rural) in two provinces in Canada. These interviews were conducted as part of a larger ethnographic study. Each transcript was analyzed by two researchers using content analysis. Results were reviewed in two focus group interviews with older adults and family caregivers. Identified themes were compared with items from two standardized assessments used in healthcare settings.

Results

Three broad themes emerged from the qualitative analysis that were not covered in the standardized assessments: informal caregiver and family considerations, insider healthcare knowledge, and patients' healthcare attitudes and experiences. The importance of these themes was confirmed through focus group interviews. Focus group participants also emphasized the importance of conducting assessments in a patient-centered way and the importance of open-ended questions.

Conclusions

A less structured interview approach may yield information that would otherwise be missed in standardized assessments. Combining both sources could yield better-informed healthcare planning and quality-improvement efforts.

http://ift.tt/2bUY0q0

Silencing transposable elements in the Drosophila germline

Abstract

Transposable elements or transposons are DNA pieces that can move around within the genome and are, therefore, potential threat to genome stability and faithful transmission of the genetic information in the germline. Accordingly, self-defense mechanisms have evolved in the metazoan germline to silence transposons, and the primary mechanism requires the germline-specific non-coding small RNAs, named Piwi-interacting RNA (piRNAs), which are in complex with Argonaute family of PIWI proteins (the piRNA–RISC complexes), to silence transposons. piRNA-mediated transposon silencing occurs at both transcriptional and post-transcriptional levels. With the advantages of genetic manipulation and advances of sequencing technology, much progress has been made on the molecular mechanisms of piRNA-mediated transposon silencing in Drosophila melanogaster, which will be the focus of this review. Because piRNA-mediated transposon silencing is evolutionarily conserved in metazoan, model organisms, such as Drosophila, will continue to be served as pioneer systems towards the complete understanding of transposon silencing in the metazoan germline.

http://ift.tt/2c3scwa

Ileostomy reversal with handsewn techniques. Short-term outcomes in a teaching hospital

Abstract

Introduction

Fecal diversion is considered an effective procedure to protect bowel anastomosis at high risk for leak. Some concerns exist regarding the risk for a significant morbidity associated to ileostomy creation itself and moreover to its closure. Surgical expertise and closure techniques are considered potential factors influencing morbidity. Aim of the study is to present a single-institution experience with ileostomy closures, in a teaching hospital, whereas ileostomy reversal is mainly performed by young residents.

Methods

A prospective database was investigated to extract data of patients who underwent loop ileostomy closure between January 2005 and December 2014. Ileostomy reversion was always realized in a handsewn fashion, performing either a direct closure (DC) or a resection plus end-to-end anastomosis (EEA). Postoperative morbidity was graded according to Clavien-Dindo classification. Outcomes after DC and EEA were compared by Fisher's exact test and Wilcoxon rank-sum test.

Results

Two hundred ninety-eight patients were included. Ileostomy reversal was performed by EEA in 236 patients (79.19 %) and by DC in 62 patients (20.81 %). Surgery was performed with a peristomal access in 296 cases (99.33 %). Incidence of anastomotic leak was 0.67 % (2/298). Overall reoperation rate was 0.34 % (1/298). Short-term overall morbidity rate was 20.47 %; but major complications (≥ grade III) occurred in only one patient (0.34 %). Mortality was nil. No significant differences in postoperative morbidity were found between the DC and EEA group.

Conclusion

Loop ileostomy reversal is a safe procedure, associated to a low major morbidity and excellent results, even if performed with a handsewn technique by supervised trainee surgeons.

http://ift.tt/2ckvP3m

Rectal prolapse traumatizes rectal neuromuscular microstructure explaining persistent rectal dysfunction

Abstract

Purpose

Internal rectal prolapse is common and correlates with age. It causes a plug-like physical obstruction and is a major cause of defecation disorder. The progressive distortion of the prolapsing rectum likely causes secondary defects in the rectal wall, which may exacerbate rectal dysfunction. We undertook a prospective observational study to detect and quantify the neurologic and histopathologic changes in the rectal wall.

Methods

We examined dorsal and ventral rectal wall specimens from consecutive patients with internal rectal prolapse undergoing stapled transanal rectal resection (STARR). We subjected specimens to histopathologic and neuropathologic assessment, including immunohistochemistry. We also recorded patients' clinical and demographic characteristics and sought correlations between these and the pathologic findings.

Results

We examined 100 specimens. The severity of rectal prolapse and the extent of descent of the perineum correlated significantly with age. Concomitant hemorrhoidal prolapse was noted in all male patients and in 79 % of female patients. Muscular and neuronal defects were detected in 94 and 90 % of the specimens, respectively. Only four specimens (4 %) were free of significant structural defects.

Conclusion

Rectal prolapse traumatizes the rectum causing neuromuscular defects. The tissue trauma is due to shearing forces and ischemia caused by the intussusception. This initiates a self-reinforcing vicious circle of physical and functional obstruction, further impairing rectal evacuation and causing constipation and incontinence. The correlation between extent of prolapse and age suggests that internal rectal prolapse can be considered a degenerative disorder. Neural and motor defects in the wall of the rectum caused by rectal prolapse are likely irreversible.

http://ift.tt/2bUUMD0

Robot-assisted versus laparoscopic surgery for lower rectal cancer: the impact of visceral obesity on surgical outcomes

Abstract

Purpose

The purpose of this study was to evaluate the advantages of robot-assisted laparoscopic surgery (RALS) for lower rectal cancer and for visceral obesity cases, which have been regarded as challenging situations in rectal cancer surgery, comparing their surgical outcomes with those of conventional laparoscopic surgery (CLS).

Methods

Patients who underwent robotic or laparoscopic total mesorectal excision for rectal cancer were included in this retrospective study. Surgical outcomes including perioperative, postoperative, and pathological data were compared between the RALS and CLS groups. Patients were stratified into obese and non-obese groups according to visceral fat area (VFA). Obesity was defined by VFA ≥130 cm².

Results

Two hundred thirty-six patients were enrolled, including 127 cases in the RALS group and 109 cases in the CLA group. A total of 82 (34.7 %) cases were categorized as VFA obese, including 52 cases in the RALS and 30 cases in the CLS groups. RALS for lower rectal cancer was associated with less blood loss (p = 0.007), a lower overall complication rate (9.4 % in RALS vs 23.9 % in CLS, p = 0.003), and shorter postoperative stay (p < 0.01) than CLS, with similar operative time and pathological results. The overall complication rate was significantly lower in the RALS group with VFA obesity; blood loss was significantly less and the postoperative stay was shorter in the RALS group with visceral obesity.

Conclusions

The present study demonstrated that RALS has some advantages in terms of surgical outcomes over CLS in challenging situations of rectal cancer surgery, such as lower rectal cancer cases and visceral obesity cases.

http://ift.tt/2c3lpmf

Association of serum vitamin D with acute lower respiratory infection in Indian children under 5 years: A case control study

2016-09-06T05-11-47Z
Source: International Journal of Contemporary Pediatrics
Deepandra Garg, Vikas K. Sharma, B. S. Karnawat.
Introduction: Acute lower respiratory infection (ALRI), primarily pneumonia and bronchiolitis, is a substantial cause of morbidity and mortality in children


http://ift.tt/2ckdWkV

Assessment of incidence, determinants and co-morbidities associated with meconium aspiration syndrome: a hospital based study

2016-09-06T05-11-47Z
Source: International Journal of Contemporary Pediatrics
Suhaim Afsar, Naresh P. Motwani*, Sudhakar C., Uma Chaturvedi.
Background: Meconium aspiration syndrome (MAS) was found to be major contributing factor towards perinatal morbidity and mortality. This condition is mainly accompanied with respiratory failure, pulmonary air leaks and pulmonary hypertension in neonates. A conservative approach of obstetrician-paediatrician combination moderates incidence of MAS and its complications. The objective of the study was to determine the incidence, determinants and co-morbidities associated with MAS in both intramural and out born admitted to the NICU and SNICU of a Chandulal Chandrakar memorial hospital located in Bhilai, Chattisgarh, India. Methods: This was a prospective study conducted in Chandulal Chandrakar memorial hospital, Bhilai from 1st September 2013 to 31st February 2015, in newborns with history of meconium stained amniotic fluid (MSAF) in both out-born and inborn units. Neonates who met inclusion criteria they were included in the study. The data were recorded in predesigned proforma. The data was analyzed using Chi square test. Level of significance of this data was set at p 2.5 kgs (80%) and common in primiparous mothers (60%) with lower segmental caesarian sections. MAS commonly seen in post -term babies (53.33%) than those of term (36.66%) or pre-term (10%) gestation. Fetal distress was the common complication observed in most of the cases (91.1%) and one death related to this was noted. At the end of 1 year there were predominantly more children (40%) who developed respiratory morbidities. Delayed development was seen among 13.3% children and transient tone abnormalities were noted in about 2% of infants. Conclusions: The overall incidence of MAS was found to have been 30% among cases of MSAF, which was relatively higher due to delayed referral. This percentage could have been reduced along with associated co-morbidities with appropriate antenatal check-ups and timely referral.


http://ift.tt/2cwngVd

Evaluation of neuro-developmental outcome among babies with meconium aspiration syndrome

2016-09-06T05-11-47Z
Source: International Journal of Contemporary Pediatrics
Suhaim Afsar, Naresh P. Motwani*, Sudhakar C., Uma Chaturvedi.
Background: Meconium aspiration syndrome (MAS) is respiratory distress in a neonates caused by the presence of meconium in the tracheobronchial airways. Despite adequate management, there is a high risk of morbidity in the form of seizures, cerebral palsy, mental retardation, respiratory problems of childhood and mortality. Hence, this study was performed in view of developmental issues concerning young infants and pre-school children as maximum brain growth happens in the first three years of life. Methods: This was a prospective study conducted in Chandulal Chandrakar memorial hospital, Bhilai from 1st September 2013 to 31st February 2015, with history of meconium stained amniotic fluid (MSAF) in both out-born and in-born neonates. Neonates after meeting inclusion criteria were included in the study. The data were recorded in pre-designed proforma. The data were analyzed using appropriate Chi square test. Level of significance was set at p 2.5 kgs (80%) and common in primiparous mothers (60%) with lower segmental caesarian sections. MAS commonly seen in post -term babies (53.33%) than those of term (36.66%) or pre-term (10%) gestation. Fetal distress was the common complication observed in most of the cases (91.1%) and one death related to this was noted. At the end of 1 year there were predominantly more children (40%) who developed respiratory morbidities. Delayed development was seen among 13.3% children, transient tone abnormalities were noted in about 2% of infants. Conclusions: The findings of the present study suggest that neonates diagnosed with MAS displayed neuro-developmental delay in13% cases. This study gave an overview of all meconium aspiration cases and the neuro-developmental outcome in these babies. However further research should be done with large sample size to confirm these findings.


http://ift.tt/2ckees7

In vivo and in vitro inhibitory activity of an ethanolic extract of Sargassum fulvellum and its component grasshopper ketone on atopic dermatitis

Publication date: November 2016
Source:International Immunopharmacology, Volume 40
Author(s): Bo-Kyeong Kang, Min-Ji Kim, Koth-Bong-Woo-Ri Kim, Dong-Hyun Ahn
The present study investigated the effect of Sargassum fulvellum ethanol extract (SFEE) on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like skin lesions in BALB/c mice. The severity of skin dermatitis, production of cytokines, and total IgE content were measured, and the histopathological features were analyzed. SFEE decreased the severity of DNCB-induced dermatitis and suppressed the serum levels of total immunoglobulin E (IgE), tumor necrosis factor (TNF)-α, and interleukin (IL)-4. In addition, SFEE reduced the production of IL-4, IL-5, and IL-13 in mice splenocytes. However, the levels of IL-10 and interferon (IFN)-γ significantly increased in mice sera and splenocytes. Histological examination revealed decreased dermal thickness and infiltration by mast cells after treatment with SFEE. Furthermore, grasshopper ketone, a compound isolated from SFEE, was found to significantly decrease cytokine production in concanavalin A-stimulated splenocytes from BALB/c mice with no cytotoxicity. Taken together, these results indicate that SFEE and the isolated grasshopper ketone have an inhibitory effect on AD by regulating immune mediators and cells and may be a potential effective alternative therapy for AD.



http://ift.tt/2bULN4B

Tumor-associated macrophages promote invasion via Toll-like receptors signaling in patients with ovarian cancer

Publication date: November 2016
Source:International Immunopharmacology, Volume 40
Author(s): Xing Ke, Shuping Zhang, Meng Wu, Jianfang Lou, Jiexin Zhang, Ting Xu, Lei Huang, Peijun Huang, Fang Wang, Shiyang Pan
Tumor-associated macrophages (TAMs) derived from peripheral blood monocytes recruit into tumor microenvironment and display functions associated with tumor progression. The mechanisms by which TAMs display roles that associated with the invasion ability of ovarian cancer have not been well investigated. In our research, we found abundant TAMs infiltrate in ovarian cancer compared with benign ovarian tumor tissues. Levels of matrix metalloproteinase (MMP)-2, MMP-9 and MMP-10, and Toll-like receptors (TLRs) signaling proteins were evaluated in ovarian cancer. The high level of TAMs was associated with metastasis and advance of patients with ovarian cancer. TAMs and ovarian cancer cell line SKOV3 were cocultured in vitro, MMPs level and the invasion ability of SKOV3 cells were significantly up-regulated. The coculture process was correlated with the activation of TLRs signaling and downstream nuclear factor (NF)-κB p65 and microtubule-associated proteins (MAPs) kinases pathway in SKOV3. In addition, pre-incubation with TLRs signaling inhibitors remarkably suppressed invasion ability of SKOV3. Levels of TLRs signaling pathways proteins were also down-regulated in this blocking process. These findings demonstrated that TAMs promoted up-regulation of MMP-2, MMP-9 and MMP-10 expressions and enhanced ovarian cancer cells invasion via TLRs signaling pathway. We conclude that TAMs could enhance ovarian cancer cells invasion and ultimately promote ovarian cancer progression.



http://ift.tt/2c38AZ5

Reducing blood pressure too low has risks for patients with heart disease, registry finds

http://ift.tt/2bTSua3

IJMS, Vol. 17, Pages 1487: Serum Calcium and the Risk of Breast Cancer: Findings from the Swedish AMORIS Study and a Meta-Analysis of Prospective Studies

To investigate the association between serum calcium and risk of breast cancer using a large cohort and a systematic review with meta-analysis. From the Swedish Apolipoprotein Mortality Risk (AMORIS) Study we included 229,674 women who had baseline measurements of serum total calcium and albumin. Multivariable Cox regression was used to assess the association between total and albumin-corrected calcium and breast cancer risk. For the systematic review, an electronic search of MEDLINE and EMBASE databases was performed to identify other prospective cohorts assessing the relationship between serum calcium and breast cancer risk. We pooled the results of our AMORIS cohort with other eligible studies in a meta-analysis using a random effects model. I2 test was used to assess heterogeneity. In the AMORIS study, 10,863 women were diagnosed with breast cancer (mean follow-up: 19 years). We found an inverse association between total serum calcium and breast cancer when comparing the fourth quartile to the first quartile (HR: 0.94, 95% CI: 0.88–0.99, p value for trend 0.04) and similar results using albumin-corrected calcium. In the systematic review, we identified another two prospective cohorts evaluating pre-diagnostic serum total calcium and breast cancer. Combining these studies and our findings in AMORIS in a meta-analysis showed a protective effect of serum calcium against breast cancer, with a summary RR of 0.80 (95% CI: 0.66–0.97). No substantial heterogeneity was observed. Our findings in AMORIS and the meta-analysis support an inverse association between serum calcium and breast cancer risk, which warrants mechanistic investigations.

http://ift.tt/2cgmbjB

IJMS, Vol. 17, Pages 1489: Escaping Antiangiogenic Therapy: Strategies Employed by Cancer Cells

Tumor angiogenesis is widely recognized as one of the "hallmarks of cancer". Consequently, during the last decades the development and testing of commercial angiogenic inhibitors has been a central focus for both basic and clinical cancer research. While antiangiogenic drugs are now incorporated into standard clinical practice, as with all cancer therapies, tumors can eventually become resistant by employing a variety of strategies to receive nutrients and oxygen in the event of therapeutic assault. Herein, we concentrate and review in detail three of the principal mechanisms of antiangiogenic therapy escape: (1) upregulation of compensatory/alternative pathways for angiogenesis; (2) vasculogenic mimicry; and (3) vessel co-option. We suggest that an understanding of how a cancer cell adapts to antiangiogenic therapy may also parallel the mechanisms employed in the bourgeoning tumor and isolated metastatic cells delivering responsible for residual disease. Finally, we speculate on strategies to adapt antiangiogenic therapy for future clinical uses.

http://ift.tt/2cglvuF

IJMS, Vol. 17, Pages 1481: Diabetes and Hypertension Consistently Predict the Presence and Extent of Coronary Artery Calcification in Symptomatic Patients: A Systematic Review and Meta-Analysis

Background: The relationship of conventional cardiovascular risk factors (age, gender, ethnicity, diabetes, dyslipidaemia, hypertension, obesity, exercise, and the number of risk factors) to coronary artery calcification (CAC) presence and extent has never before been assessed in a systematic review and meta-analysis. Methods: We included only English language studies that assessed at least three conventional risk factors apart from age, gender, and ethnicity, but excluded studies in which all patients had another confirmed condition such as renal disease. Results: In total, 10 studies, comprising 15,769 patients, were investigated in the systematic review and seven studies, comprising 12,682 patients, were included in the meta-analysis, which demonstrated the importance of diabetes and hypertension as predictors of CAC presence and extent, with age also predicting CAC presence. Male gender, dyslipidaemia, family history of coronary artery disease, obesity, and smoking were overall not predictive of either CAC presence or extent, despite dyslipidaemia being a key risk factor for coronary artery disease (CAD). Conclusion: Diabetes and hypertension consistently predict the presence and extent of CAC in symptomatic patients.

http://ift.tt/2coPbDg

IJMS, Vol. 17, Pages 1488: Drug, Herb, and Dietary Supplement Hepatotoxicity

The past decade has witnessed drugs, herbs, and dietary supplements share the common feature of potential liver injury in a few susceptible individuals.[...]

http://ift.tt/2cgls1X

IJMS, Vol. 17, Pages 1490: The Ultimaster Biodegradable-Polymer Sirolimus-Eluting Stent: An Updated Review of Clinical Evidence

The Ultimaster coronary stent system (Terumo Corporation, Tokyo, Japan) represents a new iteration in drug-eluting stent (DES) technology that has recently received the Conformité Européenne (CE) mark approval for clinical use. The Ultimaster is a thin-strut, cobalt chromium, biodegradable-polymer, sirolimus-eluting coronary stent. The high elasticity of the biodegradable-polymer (PDLLA-PCL) and the abluminal gradient coating technology are additional novel features of this coronary device. The Ultimaster DES has undergone extensive clinical evaluation in two studies: The CENTURY I and II trials. Results from these two landmark studies suggested an excellent efficacy and safety profile of the Ultimaster DES across several lesion and patient subsets, with similar clinical outcomes to contemporary, new-generation DES. The aim of this review is to summarize the rationale behind this novel DES technology and to provide an update of available evidence about the clinical performance of the Ultimaster DES.

http://ift.tt/2cgnpLC

Effect of drug physicochemical properties on drug release and their relationship with drug skin permeation behaviors in hydroxyl pressure sensitive adhesive

Publication date: 10 October 2016
Source:European Journal of Pharmaceutical Sciences, Volume 93
Author(s): Chao Liu, Peng Quan, Liang Fang
The aim of this study was to investigate the influence of drug physicochemical properties on drug release behaviors and their relationship with skin permeation behaviors, which provided transdermal enhancement strategies for the design of transdermal drug delivery system. Six model drugs with different physicochemical properties were selected and hydroxyl pressure sensitive adhesive (PSA) was synthesized. Horizontal diffusion cell was used to evaluate drug release and skin permeation behaviors. The relationship between physicochemical properties and release behaviors was conducted with regression analysis. Release behavior of 0.25% drug loading was linear related with polar surface area, which represented the hydrogen bond. Release behavior of 2.0% drug loading was dependent on the polarizability and log P, which represented dipole-dipole interaction and lipophilicity, respectively. According to the results of Fourier transform infrared spectroscopy, it was inferred that hydrogen bond was limited in controlling release of drug due to the limited quantity of bonding site, thus dipole-dipole interaction and log P became dominate control factors. Combining the drug release study and drug skin permeation study, it was concluded that drugs with different physicochemical properties should be applied with different transdermal enhancement strategies, which was useful for the design of transdermal drug delivery system.

Graphical abstract

http://ift.tt/2c7CzBN

Stability of folic acid under several parameters

Publication date: 10 October 2016
Source:European Journal of Pharmaceutical Sciences, Volume 93
Author(s): Amirah Mohd Gazzali, Mathilde Lobry, Ludovic Colombeau, Samir Acherar, Henri Azaïs, Serge Mordon, Philippe Arnoux, Francis Baros, Régis Vanderesse, Céline Frochot
Folic acid is a small molecule, also known as vitamin B9. It is an essential compound involved in important biochemical processes. It is widely used as a vector for targeted treatment and diagnosis especially in cancer therapeutics. Nevertheless, not many authors address the problem of folic acid degradation. Several researchers reported their observations concerning its denaturation, but they generally only took into account one parameter (pH, temperature, light or O2etc.). In this review, we will focus on five main parameters (assessed individually or in conjunction with one or several others) that have to be taken into account to avoid the degradation of folic acid: light, temperature, concentration, oxygen and pH, which are the most cited in the literature. Scrupulous bibliographic research enabled us to determine two additional degradation factors that are the influence of singlet oxygen and electron beam on folic acid stability, which are not considered as among the prime factors. Although these two factors are not commonly present as compared to the others, singlet oxygen and electron beams intervene in new therapeutic technologies and must be taken in consideration for further applications such photodynamic or X-rays therapies.

Graphical abstract

http://ift.tt/2c7BERQ

Use of Permeapad® for prediction of buccal absorption: A comparison to in vitro, ex vivo and in vivo method

Publication date: 10 October 2016
Source:European Journal of Pharmaceutical Sciences, Volume 93
Author(s): Hanady Ajine Bibi, René Holm, Annette Bauer-Brandl
The present work explores the usefulness of Permeapad® for prediction of buccal absorption. Permeability studies with the model drug metoprolol were carried out using the Permeapad® barrier at pH values 7.4; 8.5; 9.0, and 9.5. It was confirmed that Permeapad® can withstand these conditions, and as expected, a clear increase in permeability was found with increasing pH. The permeation results across Permeapad® were compared to published in vitro, ex vivo and in vivo studies for the same formulations. Results showed that the permeability of metoprolol using the Permeapad® barrier correlated very well to both in vitro and ex vivo studies, (r²=0.98 and 0.97), respectively. Furthermore, excellent in vitro in vivo correlation IVIVC (r²=0.98) was obtained when comparing apparent permeability coefficient to the absolute bioavailability of metoprolol administered buccally to mini-pigs. Results indicate that Permeapad® can be used to mimic the buccal absorption of metoprolol as a faster and less laborious method as compared to any of the other mentioned methods.

Graphical abstract

http://ift.tt/2c7BVEe