Osmotic Agent Research Articles

Non-pharmacological strategies to treat irritable bowel syndrome: 2022 update.

Irritable bowel syndrome (IBS) is a chronic functional disorder characterized by abdominal pain associated with changes in stool frequency or form, in absence of organic disease. The treatment of IBS is often challenging and should be individually adjusted according to the prevalent symptomatology. Pharmacological treatment for IBS with diarrhea includes peripheral opioid agonists, bile acid sequestrants and antibiotics, while IBS with constipation can be treated with soluble fibers, osmotic agents or prokinetics. In case of abdominal pain, the available pharmacological options are antispasmodics, peripheral opioid agonists or antidepressants. Along with pharmacotherapy, non-pharmacological interventions should be considered as they can play an important role in symptom control. The first-line approach includes lifestyle modifications and dietary advice. Microbiota manipulation through probiotics, prebiotics and symbiotics is a widely used strategy, although the evidence upon the most effective among these in specific IBS subtypes is still unclear. Fecal microbiota transplantation is still in experimental phase for IBS, but it is giving promising results. Psychological therapies may be effective in patients with IBS, despite their application can be limited by long duration, high costs and poor patient's acceptance. Alternative medicine approaches, such as acupuncture, body relaxation techniques, dietary supplements or Chinese herbs, have been proposed; however, the evidence upon their efficacy and safety is still controversial.

Effect of osmotic dehydration with different osmosis agents on water status, texture properties, sugars, and total carotenoid of dehydrated yellow peach slices.

The water status, texture properties, sugars, and total carotenoid of dehydrated yellow peach slices pretreated with or without osmotic dehydration (OD) combined with heat pump drying were studied. In this study, different osmotic agents were used, namely, sucrose and isomaltooligosaccharide (IMO) with 30 °Brix for 1, 3, and 5h. Results showed that the dehydrated samples pretreated by sucrose-OD with the best shape and cell structure showed lower hardness compared to the dehydrated yellow peach slices with IMO-OD pretreatment and without OD pretreatment. Notably, the highest total carotenoid content was found in dehydrated yellow peach slices pretreated by IMO-OD, followed by samples without OD, and samples with sucrose-OD pretreatment. In addition, the lowest aW (0.517) was obtained in samples with IMO-OD for 5h, which was beneficial for storage. The assessment of water status and total carotenoid content of dehydrated yellow peach slices showed that IMO-OD pretreatment could better improve the quality of dehydrated fruits. Moreover, the use of IMO in OD treatment was a good alternative to sucrose.

Assessment of Parameters to Apply Osmotic Dehydration as Pretreatment for Improving the Efficiency of Convective Drying of Cassava Bagasse

This manuscript corresponds to exploratory research carried out to evaluate and define the operating parameters for applying osmotic dehydration (OD) as pretreatment for efficiency improvement in the convective drying of cassava bagasse, providing a methodology to apply these combined techniques, not only for cassava bagasse but also to serve as a reference for its use in other high-moisture agro-industrial residues. Operating factors significant for moisture loss during OD were determined through sieving analysis. Adequate levels and operating conditions were determined for OD and subsequent drying (osmotic agent concentration, solution-to-sample ratio, agitation speed, immersion time, required draining mesh, draining time, drying temperature, and drying air speed). It was established that an osmotic treatment was able to reduce the moisture of cassava bagasse from 87.7% to 28.94% and subsequent drying time by approximately 38.8%. These results allow the use of these combined techniques for drying cassava bagasse, which in turn, open a research agenda for its application in other agro-industrial residues, contributing to its handling, revaluation, and development of a sustainable agro-industry.

In Vitro Conservation through Slow Growth Storage Technique of Fruit Species: An Overview of the Last 10 Years

Plant genetic resources conservation may be a potential option for the improvement of agricultural crops through modern biotechnologies, and in vitro conservation is a tool available to safeguard plant biodiversity. Ex situ conservation of plant genetic resources using the in vitro procedures is in progress in many countries. The slow growth storage (SGS) technique is a valid in vitro approach to preserve several vegetatively propagated species by controlling the growth and development of plantlets, economizing storage space and labor and reducing costs. Moreover, SGS prolongs the timing between subcultures, lowers the risk of losing germplasm through handling errors, such as contamination problems, and decreases the risk of genetic instability due to the reduction in the number of subcultures. SGS is applied by considering different factors: temperature, light or darkness conditions, medium composition, including mineral or sucrose concentrations, and the presence/absence of plant growth regulators, osmotic agents and growth inhibitors. SGS protocols for some fruit species have been well defined, others require additional research. The present review focuses on the effect of several factors that influence the SGS of in vitro shoots derived from temperate and tropical fruit species during the last ten years.

A Stress Hub in Scedosporium apiospermum: The High Osmolarity Glycerol (HOG) Pathway

Scedosporium species are opportunistic filamentous fungi found in human-impacted areas. Clinically relevant species, such as S. apiospermum, rank as the second most frequent colonizers of the airways of patients with cystic fibrosis (CF), which are characterized by persistent oxidative stress. This raises the question of how Scedosporium species abate conditions imposed in hostile environments. Since the High Osmolarity Glycerol (HOG) pathway plays a central role in fungal adaptation to stress, we aimed to pheno-profile the involvement of the pathway in response to stress in S. apiospermum using Western blot. We show for the first time that a wide range of stress distinctively activates the HOG pathway in S. apiospermum, including oxidants (H2O2, menadione, cumene hydroperoxide, diamide, paraquat, and honokiol), osmotic agents (sorbitol and KCl), cell-wall stress agents (caffeine, calcofluor white, and Congo Red), heavy metals (cadmium and arsenite), fungicides (fludioxonil and iprodione), antifungals (voriconazole and amphotericin B), and acid stress (pH 4). We suggest that the function of the HOG pathway as a general stress regulator is also conserved in S. apiospermum.

ROLE OF QUALITY BY DESIGN FOR THE OPTIMIZATION OF PUSH PULL OSMOTIC PUMP OF S-METOPROLOL SUCCINATE

The present research was focus on the preparation and evaluation of push pull osmotic pump of S-metoprolol succinate based on Quality by Design (QbD) approaches. For preparation of push pull osmotic pump, pull layer of S-metoprolol succinate was prepared using low molecular weight Polyox by wet granulation. Push layer containing higher molecular weight polyox and sodium chloride as osmotic agents were prepared by wet granulation. Both layers were compressed to get bilayer tablets and these bilayer tablets were coated with cellulose acetate, which act as a semipermeable membrane, and polyethylene glycol, which act as pore former. Extended release coated tablets were laser drilled on drug layer side to allow delivery of drug. The formulation was optimized using a center composite design (CCD). The effect of different drilled diameter on drug release was also evaluated. Extended release coating (%), concentration of sodium chloride (%w/w) and cellulose acetate : PEG 3350 ratio impact on drug release was optimized using center composite design (CCD). 20% Extended release coating. 20% w/w concentration of sodium chloride, and 90:10 cellulose acetate : PEG 3350 ratio gave zero order release (R2 value greater than 0.9) up to 20 h. Push pull osmotic pump of S-metoprolol succinate was successfully developed using low molecular weight polyox in pull layer and higher molecular weight of polyox in push layer.

Oral Lactulose – A Safe and Effective Strategy for the Management of Constipation in Individuals with Impaired Glucose Tolerance and Diabetes

Lactulose, either as crystals or liquid syrup, is a frequently prescribed osmotic laxative agent in patients with diabetes mellitus (DM). During the manufacturing process, carbohydrate impurities can arise which could increase blood glucose levels with a possible impact on glycemic control. This important issue has now been addressed for the first time in individuals with type 2 DM. A recent RCT confirmed that there is no need to consider carbohydrate impurities in oral lactulose products administered at the recommended doses of 20 g/day and 30 g/day for blood glucose management.

A UNIQUE CASE OF ALLERGIC URTICARIA AND ANGIOEDEMA SECONDARY TO ICODEXTRIN

<h3>Introduction</h3> Icodextrin, a starch-derived glucose polymer, is an osmotic agent used to enhance peritoneal dialysis. Icodextrin has been reported to cause an exfoliative and maculopapular rash, but to our knowledge, there is no prior description of icodextrin causing urticaria or angioedema. We present a novel adverse reaction to icodextrin with findings concerning for an IgE-mediated reaction. <h3>Case Description</h3> A 43-year-old male with a history of end-stage renal disease secondary to focal segmental glomerulonephritis on peritoneal dialysis presented to the emergency department with angioedema and urticaria. He had no history of food allergy or chronic urticaria. Four days prior to his presentation, he was started on a "purple bag" dialysis solution containing icodextrin to enhance his peritoneal dialysis. Twenty-four hours after his first dialysis exchange using the "purple bag" solution, he developed diffuse urticaria that progressed to angioedema of his lips (<b>Figure 1</b>). In the emergency department, he was given an intramuscular injection of epinephrine 0.3 mg, intravenous diphenhydramine 50 mg, methylprednisolone 125 mg, and famotidine 20 mg which resulted in complete resolution of his symptoms. The "purple bag" dialysis exchanges were discontinued, and he has not had any recurrence of the urticaria and angioedema since then. <h3>Discussion</h3> Our presented patient highlighted a probable IgE-mediated allergic reaction to icodextrin or alternatively a direct mast cell degranulation secondary to the osmotic effect of icodextrin. While further investigation with skin testing can help to discern the nature of this immediate reaction, physicians should be aware of this possible reaction when prescribing icodextrin for peritoneal dialysis.

Angle-closure glaucoma

Angle-closure glaucoma is arare form of glaucoma characterized by anarrow or an occlusion of the anterior chamber angle and subsequently an obstruction of the outflow of aqueous humor resulting in an increase in intraocular pressure. Symptoms can include severe eye pain and/or headache, blurred vision, amedium-sized and rigid pupil, conjunctival hyperemia, and nausea. Treatment options include pressure-lowering topical and systemic medications as well as surgical interventions, especially cataract surgery and laser iridotomy. Besides parasympathomimetics (pilocarpine), all topical antiglaucoma medications can principally be used (beta-receptor antagonists, carbonic anhydrase inhibitors, alpha‑2 selective adrenergic antagonists, prostaglandins and prostaglandin analogues). Carbonic anhydrase inhibitors and osmotic agents (e.g., mannitol) can be systemically used.

Computational modelling of cerebral oedema and osmotherapy following ischaemic stroke

In ischaemic stroke, a large reduction in blood supply can lead to the breakdown of the blood brain barrier and to cerebral oedema after reperfusion therapy. Cerebral oedema is marked by elevated intracranial pressure (ICP), tissue herniation and reduced cerebral perfusion pressure. In clinical settings, osmotherapy has been a common practice to decrease ICP. However, there are no guidelines on the choice of administration protocol parameters such as injection doses, infusion time and retention time. Most importantly, the effects of osmotherapy have been proven controversial since the infusion of osmotic agents can lead to a range of side effects. Here, a new Finite Element model of brain oedema and osmotherapy is thus proposed to predict treatment outcome. The model consists of three components that simulate blood perfusion, oedema, and osmotherapy, respectively. In the perfusion model (comprising arteriolar, venous, and capillary blood compartments), an anatomically accurate brain geometry is used to identify regions with a perfusion reduction and potential oedema occurrence in stroke. The oedema model is then used to predict ICP using a porous circulation model with four fluid compartments (arteriolar blood, venular blood, capillary blood, and interstitial fluid). In the osmotherapy model, the osmotic pressure is varied and the changes in ICP during different osmotherapy episodes are quantified. The simulation results of the model show excellent agreement with available clinical data and the model is employed to study osmotherapy under various parameters. Consequently, it is demonstrated how therapeutic strategies can be proposed for patients with different pathological parameters based on simulations.

FgLEU1 Is Involved in Leucine Biosynthesis, Sexual Reproduction, and Full Virulence in Fusarium graminearum.

Fusarium head blight (FHB) caused by Fusarium graminearum is a significant disease among cereal crops. In F. graminearum, biosynthesis of leucine, which is a branched chain amino acid, is achieved by converting α-isopropylmalate to β-isopropylmalate catalyzed by isopropylmalate isomerase encoded by LEU1. Considering the potential for targeting this pathway by fungicides, we characterized the gene FgLEU1 (FGSG-09589) in the Fusarium graminearum genome using bioinformatics methods. For functional characterization, we constructed a deletion mutant of FgLEU1 (ΔLEU1) through homologous recombination. Compared with the wild-type strain PH-1, ΔLEU1 showed slower colony growth and fewer aerial mycelia. Leucine addition was needed to ensure proper mutant growth. Further, ΔLEU1 showed decreased conidial production and germination rates, and could not produce ascospores. Moreover, ΔLEU1 showed complete loss of pathogenicity and reduced ability to produce deoxynivalenol (DON) and aurofusarin. Upstream and downstream genes of FgLEU1 were significantly upregulated in ΔLEU1. Contrary to previous reports, the deletion mutant was more resistant to osmotic stress and cell wall-damaging agents than the wild-type. Taken together, FgLEU1 plays a crucial role in leucine synthesis, aerial mycelial growth, sexual and asexual reproduction, pathogenicity, virulence, and pigmentation in Fusarium graminearum, indicating its potential as a target for novel antifungal agents.

Effect of Sun Drying on Osmotic Dehydration of Beetroot (Beta vulgaris L.)

An Experiment was conducted at the Postharvest laboratory, Department of Horticulture entitled with “Effect of osmotic dehydration of beetroot (Beta vulgaris L.) under sun drying” during the year 2021-2022 to determine the effect of sun drying on osmotic dehydration of beetroot slices for its evaluation of physio-chemical contents, shelf life, and sensory evaluation during total 60 days of storage period and to work out on the economics In this study, 10 treatments with varying amounts of salt, honey, sugar, and K2S2O5 were used, with 4 replications (10 days, 30 days, 45 days, and 60 days) of storage periods at ambient temperature. On the basis of results obtained during the investigation the best osmotic agent for drying of beetroot slice was T7 Treated beetroot slices (Sugar 200g/Kg + K2S2O5 0.5%) + Sun drying of beetroot slices) with pH (6.30), TSS (11.46), fat content (0.28), Protein content (2.41), weight (92.5g). T7 (Treated beetroot slices (Sugar 200g/Kg + K2S2O5 0.5%) + Sun drying of beetroot slices) was found to have the highest value for reducing sugar content, Flavour and Taste score, and overall acceptability. Treatment T7 also had the highest benefit-cost ratio (1.94).

Pretreatments, dehydration methods and packaging materials: effects on the nutritional quality of tomato powder: a review

Pretreatments and drying are commonly used before drying tomatoes to inactivate enzymes, improve the drying process, and improve the quality of dried tomato powders. In this review, the effects of different pretreatments (osmotic solutions), dehydration methods, and packaging materials on the quality attributes of tomato powder were summarized. These include pretreatments and osmotic agent solutions (potassium metabisulfite, calcium chloride, sodium metabisulphite, ascorbic acid, citric acid, sodium chloride, and sodium benzoate), thermal blanching (steam blanching and hot water) and non-thermal-processes-like-freezing, sulfuring, etc. and drying methods (oven, sun, and indirect solar dryer). The tomato powders were dried to preserve, store, and transport them. Drying implies not only physical changes, which the consumer can easily detect through visual inspection but also chemical modifications. These are responsible for alterations in color, flavor, and nutritional value, which compromise the overall quality of the final tomato powder. Maximum lycopene, vitamin A, and C contents were found in freeze-dried and direct sundried than samples dried using other methods at low drying temperatures. Freeze driers showed in keeping the nutritional quality of tomato powder with a combination of different pretreatments. Different pretreatments including osmotic agent solutions have their own merits and demerits for the final tomato powder. To overcome the drawbacks of nutritional quality, non-thermal pretreatment categories may be a better alternative to thermal blanching, and more fundamental research is required for better design and scale-up.

Formulation and Evaluation of Extended-Release Tablets of Oxybutynin HCL by Push-Pull Technology

The objective of this study was to formulate and evaluate Extended-release oxybutynin chloride tablets using a push-pull osmotic pump system. Oxybutynin HCL is a muscarinic antagonist used for the treatment of overactive bladder with symptoms of urinary incontinence, urgency, and frequency. PPOP are used to deliver drugs that are highly soluble in water. The drug is located in the upper compartment along with osmogent while the lower compartment consists of polymeric osmotic agents. The push pull technique has been formulated in the form of double-layer tablets by wet granulation. The nine formulations were prepared using oxybutynin chloride, HPMC, polyethylene oxide, Nacl, and other excipients, lubricants, and colouring agents. The tablets are coated with a semi-permeable membrane (cellulose acetate), followed by a film coating. The pre-compression parameters (Bulk density, tapped density, Carr’s index, Hausner ratio, and angle of repose) and post-compression parameters of the extended-release tablets (Hardness, friability, weight variation, thickness, and drug content) were all within limits. An FTIR study showed no interaction between API and HPMC and all excipients at the molecular level. In vitro release studies in 0.1 N HCl, and 6.0 phosphate buffer showed that the optimized F5 formulation extended the drug release by 93% after 24 h and the release profile was similar to a product from an innovator.

Cryo-derived plants through embryogenesis showed same levels of vinblastine and vincristine (anticancer) in Catharanthus roseus and had normal genome size

Cryopreservation of rare plant materials is an important approach for preserving germplasms and is a good added concept to tissue banking. The preservation of embryogenic cell suspensions is even more valuable as the tissues facilitate in producing millions of embryos, plantlets and generates transgenics en masse. Catharanthus roseus is a medicinally important plant that produces a variety of anticancerous phytocompounds and needs conservation of alkaloid producing cell lines. In this study, embryogenic tissue banking has been attempted in C. roseus by the two-step cryopreservation method combining cryoprotection and dehydration. Prior to plunging into liquid nitrogen (LN), the tissues were exposed to osmotic—and cryoprotective agents. Two osmotic agents (sugar and sorbitol) and three cryoprotective compounds, polyethylene glycol (PEG), dimethyl sulfoxide (DMSO) and glycerol were used at varying concentrations to protect cells from freezing damages. Both sucrose and sorbitol increased callus biomass post-cryopreservation; the influence of sucrose was however, more prominent. Embryogenic tissue treated in medium with 0.4 M sucrose for 2 days followed by 5% PEG for 2 h showed maximum viability before (83%) and after (55%) cryopreservation, high regrowth percentage (77%) and produced an average 9 cell colonies per Petri dish. Additionally, dehydration (1–5 h) was tested to reduce water content for improving viability and regrowth of cryopreserved embryogenic cells. Among the various tested cryoprotective conditions, the highest (72%) viability was observed following the combination of treatments with 0.4 M sucrose (2 days),10% PEG (2 h) and dehydration (2 h). Maximum regrowth percentage (88%) and 12 colonies/petri dish was noted in combination of 0.4 M sucrose + 5% PEG. The cryopreserved calli differentiated into somatic embryos (52.78–54.33 globular embryos/callus mass) in NAA (0.5 mg/l) and BAP (0.5–1.0 mg/l) added media. Plantlets were successfully regenerated from cryopreserved tissue and the 2C DNA was estimated through flow cytometry. The genome size of cryopreserved regenerant was 1.51 pg/2C, which is similar to field-grown Catharanthus plants. Vinblastine and vincristine levels were nearly the same in mother plant’s and frozen (cryopreserved) leaf tissue. The post cryopreservation embryogenesis protocol may be used for continuous production of plants for future applications.

S571 Knowledge and Utilization of Laxatives in the Inpatient Setting: A Resident Survey

Introduction: Constipation has become a major problem with increasing prevalence, especially in the current era of opioid use. It is often under-recognized in the hospital setting due to lack of universally accepted diagnostic criteria. The aim of this study is to understand the practice of prescribing laxatives among internal medicine residents at our hospital. Methods: A 12-question survey was developed on laxative use in hospitalized patients. The survey was emailed to all internal medicine residents at a university hospital center in Washington, DC. After a two-week duration, responses and results were analyzed. Results: A total of 81 internal medicine residents were emailed the survey, of which 55 responded. Among the risk factors, polypharmacy (36%) was considered as the highest risk for constipation compared to having chronic medical conditions, immobility, dehydration and aging. Although 93% of respondents were aware of the common risk factors of constipation, only 63% were cognizant of prophylactic laxative therapy. Surface active agents (docusate) was the preferred laxative (53%) while the least ordered was an osmotic agent (7%). More than half of the residents (55%) ordered laxatives as needed than as a scheduled medication. In hospitalized patients on opioid medications, 85% of respondents had a low threshold to start prophylactic laxatives, and the majority considered stimulants over osmotic laxatives (44% vs. 5.8% respectively). Based on sub-analysis, third years were more aware of contraindications to prescribing laxatives compared to interns and second years (83% vs. 76% & 64% respectively). Overall, 67% of residents were confident in prescribing laxatives in hospitalized patients. Conclusion: Based on our study, residents were aware of risk factors of constipation but still two-thirds of them were not confident in prescribing laxatives. Osmotic agents were least preferred among residents though there are evolving expert opinions favoring its use. Overall, we encourage future research on developing a systematic approach for managing constipation and broadening the knowledge on laxative use in the hospital setting.

Microwave drying of sweet potato: Drying kinetics and energetic analysis

The shelf life of the sweet potato is short due to its high water activity. Therefore, preservative techniques are mandatory. In this sense, the effects of osmotic dehydration (OD) as pretreatment, two different osmotic agents (OA), sucrose and sorbitol, and microwave power density (PD) on the drying kinetics of sweet potato slices (SPS) were studied. The SPS were immersed (pretreated) or not (untreated) in an osmotic solution at aw = 0.900. The samples were placed in the microwave and the drying proceeded until the moisture content was 0.20 ± 0.02 kg water/kg. The results showed that drying time, effective diffusivity, and specific energy consumption (SEC) increased with both increasing the microwave PD and employing OD. The effective diffusivity and SEC ranged from 5.701 × 10-10 to 5.218 × 10-9 m2/s and from 7.702 MJ/kgwater to 15.608 MJ/kgwater, respectively. An adapted model was achieved for describing the drying behavior and presented suitable adjustments. According to the results, 10W/g - sucrose must be selected for drying SPS. Drying time, SEC and η at this level were 480 s, 7.702 MJ/kgwater and 29.30%, respectively

S165 Impact of Patient Subgroups on the Efficacy and Safety of Methylnaltrexone for Opioid-Induced Constipation in Patients With Advanced Illness

Introduction: Methylnaltrexone (MNTX) is a peripherally acting µ-opioid receptor antagonist indicated for opioid-induced constipation (OIC) in patients with advanced illness who are receiving palliative care and in patients with chronic noncancer pain. We investigated if baseline patient characteristics impact the safety and efficacy of MNTX in those with advanced illness and OIC. Methods: This analysis pooled data from 2 randomized, double-blind, placebo (PBO)-controlled studies (study 302–NCT00402038; study 4000‒NCT00672477) in patients with advanced illness, including cancer. Study 302: Patients were randomized to receive subcutaneous (SC) MNTX 0.15 mg/kg or PBO every other day (QOD) for 2 weeks, with possible dose escalation to 0.30 mg/kg at week 2. Study 4000: Patients received weight-based SC MNTX 8 mg or 12 mg QOD or PBO for 2 weeks. The proportion of patients achieving a rescue-free laxation within 4 or 24 hours after the first dose of study drug was assessed in patient subgroups stratified by baseline age (< 65 vs ≥ 65), Eastern Cooperative Oncology Group (ECOG) status (≤ 2 vs > 2), cancer status, laxative type (osmotic agents, stimulants, stool softeners), and opioid requirement (oral morphine equivalent dose < 80 mg/d, 80 ‒ < 150 mg/d, and ≥ 150 mg/d). Treatment-emergent AEs (TEAEs), gastrointestinal (GI) TEAEs, and abdominal pain were evaluated. Results: Overall, 363 patients were included in this analysis (MNTX = 178; PBO = 185). Mean age was 67.8 years in the MNTX group and 66.7 years in the PBO group; 46.8% were men across all groups. A significantly greater proportion of patients receiving MNTX achieved rescue-free laxation within 4 hours (n = 111/178, 62.4% vs n = 31/185, 16.8%, P < .0001) and 24 hours (n = 135/178, 75.8% vs n = 81/185, 43.8%, P < .0001) of the first dose vs PBO. These trends were consistent across all subgroups (Table). Most patients experienced ≥ 1 TEAE in the overall population (MNTX 82.1%; PBO 76.2%); results were similar when stratified by baseline cancer, ECOG, opioid, or laxative group (Table). More than half of TEAEs were GI in nature; abdominal pain was more common in patients receiving MNTX across subgroups. Conclusion: MNTX treatment was superior to PBO in achieving RFL within 4 and 24 hours after the first dose, irrespective of patients’ cancer status, baseline ECOG status, or baseline opioid or laxative use. MNTX remained consistently safe across different baseline clinical and demographic characteristics. Table 1. - Rescue-free laxation response and treatment-emergent events by demographic and clinical characteristics subgroup Rescue-free laxation TEAEs Within 4 hours of the first dose Within 24 hours of the first dose Patients with ≥ 1TEAE Patients with gastrointestinal TEAE Patients with abdominal pain MNTX PBO MNTX PBO MNTX PBO MNTX PBO MNTX PBO Age, n (%) < 65 years 53 (63.9) 13 (14.6) 66 (79.5) 36 (40.4) 70 (84.3) 65 (73.0) 48 (57.8) 37 (41.6) 21 (25.3) 8 (9.0) ≥ 65 years 58 (61.1) 18 (18.8) 69 (72.6) 45 (46.9) 77 (80.2) 76 (79.2) 43 (44.8) 47 (49.0) 18 (18.8) 11 (11.5) Cancer status, n (%) Cancer 74 (63.8) 17 (14.9) 88 (75.9) 53 (46.5) 102 (87.9) 91 (79.8) 67 (57.8) 57 (50.0) 28 (24.1) 11 (9.6) Noncancer 37 (59.7) 14 (19.7) 47 (75.8) 28 (39.4) 44 (69.8) 50 (70.4) 24 (38.1) 27 (38.0) 11 (17.5) 8 (11.3) Functional status, n (%) ECOG ≤ 2 52 (66.7) 18 (22.5) 60 (76.9) 42 (52.5) 67 (85.9) 58 (72.5) 43 (55.1) 37 (46.3) 23 (29.5) 8 (10.0) ECOG > 2 59 (59.0) 13 (12.4) 75 (75.0) 39 (37.1) 80 (79.2) 83 (79.0) 48 (47.5) 47 (44.8) 16 (15.8) 11 (10.5) Baseline opioid dose in OME, n (%) < 80 mg/d 24 (57.1) 7 (12.3) 29 (69.0) 24 (42.1) 30 (71.4) 42 (73.7) 16 (38.1) 26 (45.6) 7 (16.7) 5 (8.8) 80 to < 150 mg/d 24 (61.5) 8 (19.0) 29 (74.4) 22 (52.4) 37 (94.9) 31 (73.8) 22 (56.4) 17 (40.5) 8 (20.5) 6 (14.3) ≥ 150 mg/d 63 (64.9) 16 (18.6) 77 (79.4) 35 (40.7) 80 (81.6) 68 (79.1) 53 (54.1) 41 (47.7) 24 (24.5) 8 (9.3) Baseline laxative regimen, n (%) Stimulants 86 (63.2) 21 (14.1) 104 (76.5) 64 (43.0) 113 (82.5) 118 (79.2) 73 (53.3) 68 (45.6) 29 (21.2) 17 (11.4) Osmotic agents 56 (65.9) 17 (20.7) 64 (75.3) 38 (46.3) 75 (88.2) 63 (76.8) 53 (62.4) 38 (46.3) 25 (29.4) 12 (14.6) Stool softeners 58 (63.0) 15 (15.3) 69 (75.0) 46 (46.9) 72 (78.3) 78 (79.6) 42 (45.7) 46 (46.9) 18 (19.6) 12 (12.2) ECOG = Eastern Cooperative Oncology Group; OME = oral morphine equivalent dose; MNTX = methylnaltrexone; PBO = placebo; TEAE = treatment-emergent adverse event.

Effect of Coating Thickness and Polyethylene Glycol’s Molecular Weight on Diltiazem Hydrochloride Release from Controlled Porosity Osmotic Pump Tablets

The purpose of this research was to design CPOP tablets to achieve controlled delivery of diltiazem hydrochloride (DH) up to 12 hours, which is a water-soluble calcium channel blocker with a short biological half-life. Two batches of osmotic tablet cores were prepared, containing DH with mannitol as an osmotic agent (1: 1.5 ratio). The tablet cores formulation with 10 mm diameter achieved the required technical and mechanical specifications. Direct compression technique was used to prepare the tablet cores which were evaluated in terms of mechanical resistance and uniformity of dosage units, followed by spray film coating using cellulose acetate as a former polymer of the semipermeable membrane and polyethylene glycol (PEG) as a pore forming agent. Several molecular weights of PEG (6000, 1500 and 400) were used and coating thickness levels were obtained. In vitro drug release, morphology of coating surface and the effect of pH change on release rate were investigated. Most of the prepared formulations demonstrated a burst release at the initial stage, which could be controlled by increasing the coating thickness. Formulations with PEG400 as a pore former presented better controlled and less burst release than those containing PEG6000, PEG1500, or a mixture of PEG6000: PEG400 (1: 1), and the pH change did not affect the drug release except in the initial stage.

Pretreatments, Dehydration Methods and Packaging Materials: Effects on the Nutritional Quality of Tomato Powder- a review

Pretreatments and drying are commonly used before drying tomatoes to inactivate enzymes, improve the drying process, and improve the quality of dried tomato powders. In this review, the effects of different pretreatments (osmotic solutions), dehydration methods and packaging materials on quality attributes of tomato powder were summarized. These include pretreatments and osmotic agent solution (potassium metabisulfite, calcium chloride, sodium metabisulphite, ascorbic acid, citric acid, sodium chloride and sodium benzoate), thermal blanching (steam blanching and hot water) and non-thermal processes like freezing, sulfuring, etc. and drying methods (oven, sun and indirect solar dryer). The tomato powders were dried to preserve, store, and transport them. Drying implies not only physical changes, which the consumer can easily detect through visual inspection, but also chemical modifications. These are responsible for alterations in color, flavor and nutritional value, which compromise the overall quality of the final tomato powder. Maximum lycopene, vitamin A and C contents were found in freeze dried and direct sundried than samples dried using other methods in low drying temperature. Freeze driers showed in keeping the nutritional quality of tomato powder with a combination of different pretreatments. Different pretreatments including osmotic agent solutions have their own merits and demerits for the final tomato powder. To overcome the drawbacks of nutritional quality, non-thermal pretreatment categories may be a better alternative to thermal blanching, and more fundamental research is required for better design and scale-up.