A 3D in-vitro biomimicking Caco-2 intestinal permeability model-based assessment of physically modified telmisartan towards an alkalizer-free formulation development.

Efficient telmisartan delivery for hypertension management requires the incorporation of meglumine and/or sodium hydroxide as an alkalizer in the formulation. Long-term use of powerful alkalis with formulation as part of chronic therapy can cause metabolic alkalosis, ulcers, diarrhea, and body pain. Here, we aimed to design a telmisartan formulation without alkalizers. Telmisartan properties were tailor-made by microfluidizer-based physical modification. After microfluidization, telmisartan nanosuspension was lyophilized to obtain telmisartan premix powder. The optimized telmisartan nanosuspension had an average particle size of 579.85 ± 32.14 nm. The lyophilized premix was characterized by FT-IR, DSC, and PXRD analysis to ensure its physicochemical characteristics. The solubility analysis of premix showed 2.2 times, 2.3 times, and 6 times solubility improvement in 0.1 N HCl, phosphate buffer pH 7.5, and pH 6.8 compared to pure telmisartan. A 3D in-vitro Caco-2 model was developed to compare apparent permeability of API and powder premix. It showed that the powder premix was more permeable than pure API. The tablet formulation prepared from the telmisartan premix showed a dissolution profile comparable to that of the marketed formulation. The technique present herein can be used as a platform technology for solubility and permeability improvement of similar classes of molecules.

The Policy of Compulsory Large-Scale Food Fortification in Sub-Saharan Africa.

Food fortification with micronutrients was initially justified in developed countries by a lack of availability of micronutrients in staple crops, mainly due to soil exhaustion. However, in Sub-Saharan arable lands, soil fatigue is not predominant, and communities consume mostly home-grown, organic, non-processed crops. Sub-Saharan food systems are nevertheless deeply entwined with food insecurity, driver of illnesses. Family production can promote subsistence, food stability, and self-sufficiency, the main SSA setback being the vicious cycle of poverty and the lack of dietary variety, contributing to malnutrition. Poverty reduction and women's education are significant strategies for reducing child and adolescent undernourishment. Fortification of foods consumed daily by individuals makes sense and can minimize, if not entirely, eliminate deficiencies. Compulsory mass fortification of foods in Sub-Saharan Africa (SSA) with single micronutrients is, however, controversial since they work in synergy among each other and with the food matrix, for optimal absorption and metabolism. Since the causes of malnutrition are many, caused by diverse, unequal, and unjust food distribution, interrelated with political, social, cultural, or economic factors, education status of the population, season and climatic changes, and effectiveness of nutrition programs, just food fortification cannot solve the composite of all these elements. Further, compulsory fortification is excessive, unproductive, and likely harmful to human health, while many challenges remain in assessing the quality of available premixes. Furthermore, aiming at dietary diversification is the best approach of increasing trace element intake from commonly accessible and easily available food sources.

Premix technologies for drug delivery: manufacturing, applications, and opportunities in regulatory filing.

Active pharmaceutical ingredients (APIs) and excipients can be carefully combined in premix-based materials before being added to dosage forms, providing a flexible platform for the improvement of drug bioavailability, stability, and patient compliance. This is a promising and transformative approach in novel and generic product development, offering both the potential to overcome challenges in the delivery of complex APIs and viable solutions for bypassing patent hurdles in generic product filing. We discuss the different types of premixes; manufacturing technologies such as spray drying, hot melt extrusion, wet granulation, co-crystal, co-milling, co-precipitation; regulatory filing opportunities; and major bottlenecks in the use of premix materials in different aspects of pharmaceutical product development.

Rapid method for quantitation of seven human milk oligosaccharides in infant formula and premix.

As the evidence supporting the beneficial effects of human milk oligosaccharides (HMOs) grows, so does the commercial interest in their inclusion in infant formula products. This also requires analytical methods capable of their quantification from finished infant formula products as well as from premixed ingredients in some cases. The objective of the present study was the development and single-laboratory validation of a method that can be used for this purpose for seven HMOs: 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), difucosyllactose (DFL), 3'-sialyllactose (3'SL), 6'-sialyllactose (6'SL), lacto-N-tetraose (LNT), and lacto-N-neotetraose (LNnT). The present method uses labeling by reductive amination, with 4-aminobenzoic acid ethyl ester (benzocaine) as the labeling reagent and picoline borane as the reducing agent, then applies HPLC separation with UV detection. The seven HMOs could be analyzed from infant formula and premix samples with recoveries between 91 and 108 %, relative standard deviations of 4.3 % or lower across all replicates, and limits of quantitation between 0.001 % and 0.004 % of powder sample by weight. The method was found to be rapid and reliable, with a runtime of only 14 min per injection, in contrast to other methods found in literature which typically use nearly or more than an hour. In addition, it uses instrumentation that's readily available in most analytical laboratories.

Premix versus On-Demand Workflow Models in a Veterans Affairs Hematology/Oncology Pharmacy: Impact on Estimated Waste Costs and Patient Wait Time.

Background: The balance between reducing patient wait time and mitigating waste of parenteral products has not been well described in literature. Objective: Evaluate the patient wait times and cost-effectiveness of employing a premix versus an on-demand workflow model for compounding parenteral admixtures in a hematology/oncology infusion setting. Methods: This single center, retrospective cost analysis compiled manually documented monthly waste reports and estimated drug pricing for the institution to calculate the cost of waste during both premix and on-demand compounding workflows. Time to administration was audited for one week with both models. Results: Over a period of 28.5 months following the premix model, 564 products were documented as wasted ($1,196,014.01 in estimated drug purchasing cost). Over a period of 3 months following the on-demand model, 12 products were wasted ($34,823.98 in estimated drug purchasing cost). Switching models reduced the monthly average number of wasted products from 20 to 4 per month; the average cost of waste was reduced from $41,965.40 to $11,607.99 per month (P < .0001). Overall patient wait time from clearance until administration, excluding any recommended wait times after premedication administration (if applicable), was similar in both models: an average of 38.26 minutes in the premix model and 40.97 minutes in the on-demand model. Conclusion: Premixing parenteral admixtures was not cost effective at our institution. After resuming an on-demand compounding model, the monthly cost of waste (based on drug pricing alone) was reduced by over 70%. The wait time from clearance to treatment administration was similar in both models.

Effect of mineral-vitamin premix supplementation on behavioral, performance, hormonal, oxidative stress, and serum biochemical profiles on rutting male Camelus dromedarius in Egypt.

Introduction: The rutting period imposes a stressful condition on male camels, which results in elevated serum cortisol levels and alterations in their sexual behavior. Therefore, the current work was carried out to investigate the effect of mineral-vitamin premix supplementation on behavior, reproductive performance, hormones, serum oxidative stress profile, and other serum biochemical parameters of Camelus dromedarius during the breeding season. Methods: Fourteen mature, fertile male Camelus dromedarius were divided into two groups, a control group (n = 7) and a mineral-vitamin premix group (n = 7). The present study lasted for 95 days during the rutting period (1st February to 5th May). Each camel in the premix group received a daily diet of 50 g of mineral-vitamin premix throughout the whole rutting period, during which the frequencies and durations of the following behaviors: maintenance, posture, aggressiveness, and sexual activity were collected every 20 min. At the end of the study, blood samples were collected. Results: Results revealed that the premix group showed higher (P < 0.05) maintenance (feeding and rumination), standing, and overall sexual desire-related behavior frequency, besides more times (P < 0.001) for rumination, standing, walking, and lying while showing lower (P < 0.001) frequencies of overall aggressive behaviors than the control group. The serum concentration of malondialdehyde, nitric oxide, cortisol, blood glucose, and urea evidenced a significant decrease in the premix group compared with the control one, while significantly elevated levels of reduced glutathione, testosterone, total antioxidant capacity, triiodothyronine, and thyroxin, total protein, albumin, globulin, calcium, phosphorus, potassium, and magnesium were recorded in the premix group in comparison with the control. Conclusion: It could be concluded that daily dietary supplementation of 50 g of mineral-vitamin premix to male camels during the breeding season is necessary to overcome the oxidative stress and serum cortisol concentration with a subsequent decrease in aggressive behavior and improvement to testosterone level in blood, body condition score and body weight gain.

Quality evaluation of nutri-premix prepared by using millets and seeds of fruits and vegetables.

The objective of the present research was intended to formulate multigrain premix powder which could be utilized for the development of nutritional rich products. The multigrain premix was prepared by blending the seeds of pumpkin, jackfruit, and mango with barley, pearl millet, finger millet, sorghum, and other ingredients such as cardamom, and sugar. Before optimizing the composition of premix flour, around 8 combinations of each flour and seed powders were made to obtain the preeminent quality premix with high nutritional value. The formulation of flour was optimized on the basis of sensory analysis done by using 9-hedonic scale. The formulated multigrain premix was analysed for its nutritional and sensorial characteristics. Multigrain premix resulted in protein content of 5.35 g, carbohydrate 80.25 g, fat 6.88 g, ash 3.87 g, dietary fibres 8.67 g, calcium 73.25 mg, and iron 2.94 mg per 100 g of the mixture and many more minerals were also estimated in the given premix. Total energy was noted as 404.32 kcal. The GC-MS analysis was also performed to identify the composition of fat in terms of their saturation. Moreover, the shelf life study of multigrain premix was carried out for a period of 45 days at a temperature and relative humidity of 25 °C and 91% respectively. The overall quality of the multigrain premix was accepted in term of overall acceptability. The optimized premix was also taken for its microbiological analysis, and sensorial quality attributes to understand the shelf life study of the product when stored for longer period of time.

Stability of Bacillus and Enterococcus faecium 669 Probiotic Strains When Added to Different Feed Matrices Used in Dairy Production.

Few data are available evaluating the stability of direct-fed microbials (DFM) following their inclusion in different feed matrices. Therefore, six Exp. evaluated the recovery of bacilli spores (BOVACILLUSTM; Exp. 1 to 3) and an Enterococcus faecium DFM (LACTIFERM®; Exp. 4 to 6) when included in different feed preparations. The Bacillus-based DFM was included into pelleted feed prepared in different temperatures (75 to 95 °C), whereas both DFM were assessed in premix and milk replacer preparations. Bacillus spores and E. faecium recovery was evaluated through standard methodologies and data were reported as log10 colony forming units/gram of feed. The recovery of Bacillus spores was within the expected range and was not impacted by the temperature of pellet preparation (Exp. 1). Bacilli recovery was also stable up to 12 months in the premix and was not impacted by the temperature of milk replacer preparation. Regarding the Exp. with E. faecium (Exp. 4 to 6), its recoveries in the mineral premix and milk powder did not differ from T0 and were not impacted by the conditions of milk replacer preparation. These data are novel and demonstrate the stability of a Bacillus-based and an E. faecium-based DFM when included in different feed matrices often used in dairy production.

Effects of Malva parviflora Leafs as the Herbal Additives on Broilers Productivity.

Malva parviflora is a leafy vegetable belonging to the family Malvaceae. Medicinal plants have had several vital chemical compounds, with some biological functions. Supplementation of these plants to the animals diets lead to significant betterments in the animals' productivity and health status. This study was designed to investigate the effects of Malva parviflora as a substitute for commercial premix carrier in the poultry diets to see the response on some of the productive and economic traits in broilers. 576 one day old Ross 308 chicks were randomly divided into eight groups with three replicate (24 bird /replicate) per group. Each group was subjected to the one of the following treatments: Tr 1. (Control) contained 2.5% of diet supplemented with homemade premix (with carrier Malva parviflora weed leaves meal), Tr 2. 2.5% provimi premix, Tr 3. 2.5% Turkis hpremix, Tr 4. Dutch premix, Tr 5. 50% homemade premix + 50% provimi premix, Tr 6. 50% homemade premix + 50% Turkish, Tr 7. Homemade premix + 50% Dutch 50% Tr 8. 25% from each four types premixes. Live body weight, feed consumption, feed conversion, growth rate، Production Index، economic indicator and mortality rate averages were measured to the 5 weeks of age. Result showed that there were significant differences (P<0.05) among treatments in weight gains at all periods. Treatment 1،26،5 ،4، showed the highest weight gain at 5 weeks of age;however, Tr.3،7 showed the lowest value. There were significant differences (P<0.05) in the rate of feed consumption among treatments during the different periods. Birds in Tr.3 consumed the highest amount of feed compared with control, Also there was significant differences in feed conversion ratio among all treatment groups at all periods where, the highest value was found in (Tr.3), and the lowest value was recorded in Tr.1.At least there was large differences in cost of locally premix which recorded the cheapest and lowest value about 1300 U.S.A$ less in every ton compared with the commercial premixes.

Oral pharmacokinetics of a pharmaceutical preparation of florfenicol in broiler chickens.

Introduction: The use of florfenicol must follow particular pharmacokinetic/pharmacodynamic (PK/PD) ratios, i.e., it requires achieving serum concentrations at or slightly above the pathogen's minimum inhibitory concentration (MIC) during the dosing interval and that the ratio of area under the concentration vs. time curve (AUC)/MIC should be as high as possible (still undetermined for poultry). As an alternative to the standard soluble florfenicol that is administered to the flock through drinking water, florfenicol premix is often recommended as feed medication in Latin America. However, no particular pharmaceutical design has been proposed. Methods: This study compared the PK of two preparations of florfenicol in broiler chickens and pondered the possibility of each covering the referred PK-PD ratios as predictors of clinical efficacy. The preparations comprise a pharmaceutical form as FOLA pellets (F = bioavailability; O = optimum; and LA = long-acting) and the premix formulation. The former are small colored pellets with vehicles and absorption enhancers of florfenicol designed for long action, and the latter is the reference premix of the antibiotic. First, these two pharmaceutical forms of florfenicol were administered as oral boluses (30 mg/kg), aided by a probe. In a second trial of the dosing form, both pharmaceutical preparations of florfenicol were administered in feed and ad libitum (110 ppm; ~30 mg/kg). Results: In both cases, FOLA-florfenicol presented much higher relative bioavailability (3.27 times higher) and mean better residence time than florfenicol premix (two times high when forced as bolus dose). Consequently, FOLA-florfenicol possesses better PK/PD ratios than less sensitive pathogens, i.e., E. coli. It is proposed that if a metaphylactic treatment of a bacterial outbreak in poultry is implemented with florfenicol prepared as FOLA, better PK/PD ratios will be obtained than those of standard florfenicol premix. Discussion: Clinicians must confirm that feed consumption in the flock has not been affected by the particular disease if FOLA pellets of florfenicol are used.

Determination of burn rate affecting elements in composite solid propellant and its ingredients by microwave-induced plasma optical emission spectrometry.

A study of trace metallic elements in solid propellant and its ingredients is important and critical as they affect ballistic properties of solid rocket motor during combustion. In the present study, an attempt is made to develop a rapid, single run and cost-effective analytical technique for the routine and direct analysis of multi elements. Trace level metallic impurities (burn rate affecting elements) present in premix, cured propellant slab and propellant ingredients such as ammonium perchlorate, aluminium, aluminium oxide, dioctyladipate, hydroxy terminated polybutadiene and toluene diisoycanate sourced from different suppliers and propellant slag are determined based on a relatively recent analytical technique, microwave-induced plasma optical emission spectrometry (MIP-OES). Analytical wavelengths are selected based on the sensitivity and interference effects. Precision and accuracy of the developed test procedure for the metallic impurities are demonstrated using replicate analyses of certified calibration standards. The limit of quantification and detection of elements studied is determined. Linear regression coefficients are greater than 0.995. The results obtained demonstrate the potential of MIP-OES technique for the determination of metallic impurities of solid propellant ingredients, pre-mix, cured slab and slag of solid propellants with shortened analysis time which achieved lower detection limits, higher accuracy and better repeatability.

New Approach in the Determination of a Suitable Directionally Coarsened Microstructure for the Fabrication of Nanoporous Superalloy Membranes Based on CMSX-4.

The pore size of nanoporous superalloy membranes produced by directional coarsening is directly related to the γ-channel width after creep deformation, since the γ-phase is removed subsequently by selective phase extraction. The continuous network of the γ'-phase thus remaining is based on complete crosslinking of the γ'-phase in the directionally coarsened state forming the subsequent membrane. In order to be able to achieve the smallest possible droplet size in the later application in premix membrane emulsification, a central aspect of this investigation is to minimize the γ-channel width. For this purpose, we use the 3w0-criterion as a starting point and gradually increase the creep duration at constant stress and temperature. Stepped specimens with three different stress levels are used as creep specimens. Subsequently, the relevant characteristic values of the directionally coarsened microstructure are determined and evaluated using the line intersection method. We show that the approximation of an optimal creep duration via the 3w0-criterion is reasonable and that coarsening occurs at different rates in dendritic and interdendritic regions. The use of staged creep specimens shows significant material and time savings in determining the optimal microstructure. Optimization of the creep parameters results in a γ-channel width of 119 ± 43 nm in dendritic and 150 ± 66 nm in interdendritic regions while maintaining complete crosslinking. Furthermore, our investigations show that unfavorable stress and temperature combinations favor undirectional coarsening before the rafting process is completed.

Optimal Administration of Phosphorus Adsorbents When Using Medical Nutritional Supplements for Tube-fed Patients.

All medical enteral nutrition products contain phosphorus and when administered to patients with chronic kidney disease (CKD) and on dialysis, they lead to the risk of elevated serum phosphorus levels. Thus, serum phosphorus levels should be monitored, and phosphorus adsorbents should be used in cases of high serum phosphorus levels. In this study, we investigated the effect of phosphorus adsorbents on enteral nutrition, using Ensure Liquid®, a medical nutritional formula, for patients with CKD and those on dialysis. Additionally, we compared the effects of the simple suspension method, in which various phosphorus-adsorbing agents are suspended and mixed directly with the nutritional formula for tube administration (hereafter referred to as the "pre-mix method"), and the conventional method, in which only the phosphorus-adsorbing agents are administered separately from the nutritional formula for tube administration (hereafter referred to as the "normal administration method"). The administration of various phosphorus adsorbents using the pre-mix technique resulted in a phosphorus removal rate of 8-15% (approximately 12% on average). Therefore, through the pre-mix method, maintaining the phosphorus content of Ensure Liquid® below the daily phosphorus intake standard was possible for patients on dialysis. The pre-mix method via the simple suspension method of administering phosphorus adsorbent with Ensure Liquid® resulted in less drug adsorption to the injector and tube and a higher phosphorus removal rate than the normal administration method.

Comparison of regular with NPH insulin vs. premix insulin in children and adolescents with type 1 diabetes in a resources-limited setting: a retrospective data analysis.

OBJECTIVES: Few studies addressed the efficacy of human insulin regimens (mostly premix insulin) used in many low-and-middle income countries on glycemic control of children and adolescents with diabetes. The aim of this study was to assess the efficacy of the premix insulin on the glycated hemoglobin (HbA1c) in comparison to the regular with NPH insulin scheme. METHODS: A retrospective study was carried out from January 2020 to September 2022 on patients with type 1 diabetes aged below 18 years followed in Burkina Life For A Child program. They were categorized into three groups, on regular with NPH insulin (Group A), on premix insulin (Group B) and on regular with premix insulin (Group C). Outcome was analyzed based on HbA1c level. RESULTS: Sixty-eight patients with a mean age of 15.38 ± 2.26 years and the sex ratio (M/W) 0.94 were studied. There were 14 in Group A, 20 in Group B, and 34 patients in Group C. The mean HbA1c value in the corresponding insulin regimen was 12.8 ± 1.39%, 9.87 ± 2.18%, and 10.66 ± 2.1%, respectively. Glycemic control was better in Groups B and C than Group A (p<0.05) but there was no difference between groups B and C. CONCLUSIONS: Our results indicate that the use of premix insulin gives a better glycemic control than NPH insulin. However, further prospective study of these insulin regimens with a strengthening education strategy and glycemic control by continuous glucose monitoring and HbA1c is required to corroborate these preliminary findings.

Replacing biochar with mineral premix and its interaction with vitamin C on laying hen production and egg quality factors.

This researchers focused at how adding vitamin C (VC) to biochar and replacing it with a mineral supplement affected egg quality and laying hen performance. 50 experimental units were created from 400 laying hens using a 5 × 2 factorial treatment design (10 treatments, 5 repeats, and 8 laying hens per repetition). Biochar levels (0, 25, 50, 75, and 100% replacement with mineral supplements of diet) and VC levels (0 and 100 mg/kg of diet) were some of the studied variables. The results showed that different experimental diets had no significant effect on performance parameters (feed intake, feed conversion ratio, daily weight gain, egg weight, egg production, and egg mass) of laying hens. In the whole of experiment (50-62 weeks of age), dietary treatments had no influence on egg albumen %, Haugh unit, albumen index, yolk %, yolk index, yolk color, egg shell thickness, or egg shell ash. The results revealed that biochar, due to its availability and easy production, can replace mineral supplements in laying hens' diet, with no adverse effects on productive performance and egg quality traits.

Pharmacokinetic Similarity between Biosimilar Insulin Aspart Premix SAR341402 Mix 70/30 and Originator Insulin Aspart Mix 70/30 (NovoMix 30) in Indian Adults with Type 2 Diabetes: GEMELLI M Substudy.

Background: We compared the pharmacokinetic exposure, efficacy, safety and immunogenicity of biosimilar insulin aspart premix SAR341402 Mix 70/30 (SARAsp-Mix) with its originator NovoMix® 30 insulin aspart mix (NN-Mix) in adults with type 2 diabetes. Methods: This was a randomized, open-label, parallel-group, substudy of the phase 3 GEMELLI M trial performed in three Indian centres. Totally 13 Indian participants previously treated with premix insulin received a single subcutaneous 0.3 U/kg dose of each treatment and underwent pharmacokinetic sampling for 16 h after dosing. Participants were then treated for 26 weeks as per the main GEMELLI M trial with efficacy, safety and immunogenicity compared between groups. Results: The extent of exposure (area under the plasma concentration-time curve and maximum insulin aspart concentration) to SAR341402 insulin aspart in SARAsp-Mix and to insulin aspart in NN-Mix was similar following single doses of the allocated treatment. After 26 weeks, the mean ± SD [median] change in HbA1c from baseline was similar in both treatment groups (SARAsp-Mix -0.38% ± 1.54 [-1.00%]; NN-Mix -0.18% ± 1.97 [-0.80%]). Other efficacy endpoints, insulin dosages, anti-insulin aspart antibody response, hypoglycemia and adverse events were similar between groups. Conclusions: Our results support the findings from previous studies, that SARAsp-Mix has a similar pharmacokinetic profile to NN-Mix and provides effective glycemic control with similar safety and immunogenicity profile in Indian adults with type 2 diabetes.

Cost-Effectiveness of iGlarLixi Versus Premix BIAsp 30 in People with Type 2 Diabetes Suboptimally Controlled by Basal Insulin in the US.

INTRODUCTION: Many people with type 2 diabetes mellitus (T2DM) experience suboptimal glycemic control and require therapy advancement. This cost-effectiveness analysis was conducted to compare iGlarLixi (insulin glargine 100 U/mL plus lixisenatide) versus BIAsp 30 (biphasic insulin aspart 30) in people with T2DM suboptimally controlled with basal insulin. METHODS: The IQVIA Core Diabetes Model was used to estimate lifetime costs and outcomes for people with T2DM from a US healthcare payer perspective. Initial clinical data were based on the phase 3 randomized, open-label, active-controlled SoliMix clinical study, which compared the efficacy and safety of once-daily iGlarLixi with twice-daily BIAsp 30. Lifetime costs (US$) and quality-adjusted life-years (QALYs) were predicted, and the incremental cost-effectiveness ratio (ICER) for iGlarLixi versus BIAsp 30 was estimated; the willingness-to-pay threshold was considered to be $50,000. A subgroup analysis considered people with T2DM aged ≥ 65 years. RESULTS: Estimated QALYs gained were slightly higher with iGlarLixi compared with BIAsp 30 (9.3 vs. 9.2), with lower costs for iGlarLixi ($117,854 vs. $120,109); the ICER for iGlarLixi was therefore considered dominant over BIAsp 30 in the base case. Key drivers for cost savings were the higher dose and twice-daily administration for BIAsp 30 versus once-daily administration for iGlarLixi. The robustness of the base-case results was confirmed by sensitivity and scenario analyses. Results were similar in a subgroup of people with T2DM aged ≥ 65 years. CONCLUSION: In people with T2DM with suboptimal glycemic control on basal insulin, iGlarLixi confers improved QALYs and reduced costs compared with BIAsp 30.

IDegLira Improves Metabolic Control in Patients with Type 2 Diabetes Previously Treated with Premix Insulin.

Background: IDegLira( fixed combination of GLP 1 receptor agonist and insulin) has been shown to be effective in improving the glucoregulation in patients previously treated with oral therapy as well as individual components, GLP-1 receptor agonist or basal insulin. Objective: The aim of this study is to examine the parameters of metabolic control in patients treated with IDegLira who were previously treated with premix insulin in several daily doses and to compare them with patients whose premix insulin dose was increased. Methods: The study included 100 patients who had been previously treated with two or three daily doses of premix insulin. Half of the patients were switched to IdegLira( group I), and half (group II) had their insulin dose increased according to the clinical assessment of the physician. Fasting glucose, 2h postprandial glucose, HbA1c, BMI and insulin dose were determined at baseline and at follow-up after 6 months. Results: Patients treated with IDegLira compared to patients whose insulin dose was increased achieved significantly lower fasting glucose (p <0.001), postprandial glucose (p <0.001), HbA1c (p <0.001), BMI (p <0.001) with a significantly lower insulin dose (p <0.001). Comparison of the same parameters within the groups of patients at the beginning and after 6 months showed that patients who were switched from insulin premix to IDegLira achieved significantly lower fasting blood glucose (p <0.001), postprandial glucose (p <0.001), HbA1c (p < 0.001), BMI (p <0.001) with significantly lower insulin dose within the fixed combination (p <0.001). Patients with gradually increased insulin dose achieved significant reduction in fasting glucose (p = 0.021) and postprandial glucose (p = 0.036),but with a significantly higher insulin dose (p = 0.005). There was also a slight increase in BMI that was not statistically significant (p = 0.267). Conclusion: The obtained data suggest that switching patients from a complex insulin regimen to a fixed combination of basal insulin and GLP 1 receptor agonist in comparison to increases in insulin dose results in a significant improvement in fasting glucose, postprandial glucose, HbA1c, and BMI. The results were achieved with a significantly lower daily insulin dose.

Development and validation of a novel stability-indicating reverse phase HPLC method for the determination of sacubitril-valsartan premix stereoisomers: Cellulose tris(4-methyl benzoate) stationary phase.

A new stability indicating reverse phase HPLC method has been developed and validated as per International Conference on Harmonization guidelines for the determination of sacubitril-valsartan premix stereoisomers, namely, (2R)-valsartan, (2S,4S)-sacubitril, (2R,4S)-sacubitril, and (2R,4R)-sacubitril. Primarily, stability indicating separation study was done on reverse phase LC conditions; it was described by peak homogeneity of sacubitril-valsartan and its stereoisomers. Cellulose tris(4-methylbenzoate) packing column Chiralcel OJ-RH(150 mm × 4.6 mm), 5 µm provided better resolution than those of amylose based stationary phase's. Resolution between two arbitrary adjacent analyte was found to be more than 2.0 with 0.1% trifluoroacetic acid in water as mobile phase-A and mobile phase-B consisting of acetonitrile, methanol, and trifluoroacetic acid (90:10:0.1, v/v/v). Gradient elution was performed at a flow rate of 1.0 ml/min, column temperature 20°C, injection volume 10 µl, UV detection at 254 nm and run time was 52 min. The detector response linearity of stereoisomers found to be linear (R2  ≥ 0.9998), limit of detection (0.290 µg/ml, 0.122 µg/ml, 0.123 µg/ml, and 0.124 µg/ml), and limit of quantification (0.878 µg/ml, 0.370 µg/ml, 0.373 µg/ml, and 0.375 µg/ml), respectively. Percentage recovery was found to be 98-105. Finally, the proposed method is user friendly and can be used in bulk drugs analysis.

Efficacy, Safety, and Immunogenicity of Biosimilar Insulin Aspart Premix SAR341402 Mix 70/30 Compared with Originator Insulin Aspart Mix 70/30 in Adults with Diabetes (GEMELLI M): A Subgroup Analysis by Prior Type of Premix Insulin.

INTRODUCTION: We compared the efficacy, safety, and immunogenicity of biosimilar insulin aspart premix SAR341402 Mix 70/30 (70% intermediate SAR341402 protamine and 30% rapid SAR341402 solution) (SARAsp-Mix) with its originator NovoMix 30 insulin aspart mix (NN-Mix) in adults with type 1 or type 2 diabetes switching from different premix insulin analogs. METHODS: This phase 3, randomized, open-label, multinational, 26-week trial (GEMELLI M) enrolled 402 participants with type 1 or type 2 diabetes. At randomization, participants switched from their prestudy premix insulin NovoMix 30 (n = 341) or Humalog Mix 25/Liprolog Mix 25 (n = 61) to equivalent (1:1) doses of either SARAsp-Mix or NN-Mix at least twice daily (1:1 randomization). In this subgroup analysis, efficacy measures [change in hemoglobin A1c (HbA1c), daily insulin dose], and safety outcomes [hypoglycemia incidence, adverse events (including hypersensitivity and injection site reactions), anti-insulin aspart antibodies] of SARAsp-Mix were compared with those of NN-Mix separately according to the participants' prestudy premix insulin. RESULTS: At week 26, change from baseline in HbA1c (primary efficacy endpoint) was similar between SARAsp-Mix and NN-Mix in those participants pretreated with NovoMix 30 [least squares (LS) mean difference 0.05%, 95% confidence interval (CI) -0.195% to 0.289%] or Humalog Mix 25/Liprolog Mix 25 (LS mean difference 0.28%, 95% CI -0.279% to 0.830%) (P value for treatment-by-subgroup interaction = 0.46). In both subgroups, safety outcomes, including immunogenicity, and changes in daily insulin doses were similar between treatments over 26 weeks. CONCLUSIONS: Efficacy, safety, and immunogenicity profiles of SARAsp-Mix are similar to NN-Mix over 26 weeks in adults with diabetes irrespective of prior type of premix insulin. TRIAL REGISTRATION: EudraCT number 2017-000092-84.