GABA induces a hormonal counter-regulatory response in subjects with long-standing type 1 diabetes

IntroductionExperimentally, gamma-aminobutyric acid (GABA) has been found to exert immune-modulatory effects and induce beta-cell regeneration, which make it a highly interesting substance candidate for the treatment of type 1 diabetes (T1D). In many countries, including those in the European Union, GABA is considered a pharmaceutical drug. We have therefore conducted a safety and dose escalation trial with the first controlled-release formulation of GABA, Remygen (Diamyd Medical).Research design and methodsSix adult male subjects with long-standing T1D (age 24.8±1.5 years, disease duration 14.7±2.2 years) were enrolled in an 11-day dose escalation trial with a controlled-release formulation of GABA, Remygen. Pharmacokinetics, glucose control and hormonal counter-regulatory response during hypoglycemic clamps were evaluated at every dose increase (200 mg, 600 mg and 1200 mg).ResultsDuring the trial there were no serious and only a few, transient, adverse events reported. Without treatment, the counter-regulatory hormone response to hypoglycemia was severely blunted. Intake of 600 mg GABA more than doubled the glucagon, epinephrine, growth hormone and cortisol responses to hypoglycemia.ConclusionsWe find that the GABA treatment was well tolerated and established a counter-regulatory response to hypoglycemia in long-standing T1D. Further studies regarding not only the clinical potential of Remygen for beta-cell regeneration but also its potential use as hypoglycemic prophylaxis are warranted.Trail registration numberNCT03635437 and EudraCT2018-001115-73.

Hot Melt Coating: Development and Optimization of Controlled Release Formulation and Process of Oxcarbazepine

Hot-melt coating process (HMCP) is being developed to formulate lipid based oral controlled release formulation system for anti-epileptic drug Oxcarbazepine. Pellets containing Active ingredient in the core portion were prepared by extrusion spheronization process with use of appropriate filler and binder. These core pellets were then coated using hot-melt coating technology with different levels of solid lipid material and a hydrophilic component. Formulation and Process parameters were optimized to achieve targeted drug release profile and other target product profile with particular focus on HMCP. Quality by design (QbD) with DOE approach was used for designing and development of the formulation, by putting risk assessment (FMEA, Fish-bone diagram), screening (by Plackett Burman), and optimization (by CCC) studies. Appropriate ‘design space’ was proposed based on the optimization studies. The results demonstrated that the level of Low melting coating component and a hydrophilic component influenced the drug release rate from the formulation, and the rate of release could be optimized by varying the amount of these components in the formulation. Processing parameters like Temperature of the coating solution and atomization air, Atomization air pressure and Spray rate also affects the drug release rate and other parameters like coating efficiency and mean particle size. For optimized formulation, dissolution data model fitting was also carried out which adequately fits to Higuchi model suggesting that the drug release occurred predominantly by diffusion.

Development and Optimization of Controlled Release Formulation and Process of Levetiracetam with Hot Melt Coating Technology

Conventional coating processes are based on aqueous or organic solvent system, resulting in the lengthy and tedious processes where use and removal of solvents consumes lots of energy and resources. Also, solvent disposal is a critical issue considering environmental hazard.Hot melt coating process avoids use of solvent and is short and energy-efficient process. Here, Hot-melt coating process (HMCP) is being developed to formulate lipid based oral controlled release formulation system to deliver highly water soluble Biopharmaceutical Classification System (BCS) class-I drug Levetiracetam. Pellets containing Active ingredient in the core portion were prepared by extrusion spheronization process with use of appropriate filler and binder. These core pellets were then coated using hot-melt coating technology with different levels of lipid and a hydrophilic component. Formulation and Process parameters were optimized to achieve targeted drug release profile and other target product profile with particular focus onHMCP. Quality by design (QbD) with DOE approach was used for designing and development of the formulation, by putting risk assessment Failure Mode and Effect analysis (FMEA, Fish-bone diagram), screening (by Plackett Burman), and optimization by Central Composite Design (CCC) studies. Appropriate ‘design space’ was proposed based on the optimization studies. The results demonstrated that the level of Low melting coating component and a hydrophilic component influenced the drug release rate from the formulation, and the rate of release could be optimized by varying the amount of these components in the formulation. Processing parameters like Temperature of the coating solution and atomization air, Atomization air pressure and Spray rate also affects the drug release rate and other parameters like coating efficiency and mean particle size. For optimized formulation, dissolution data model fitting was also carried out which adequately fits to Higuchi model suggesting that the drug release occurred predominantly by diffusion.

Using a reactive emulsifier to construct simple and convenient nanocapsules loaded with lambda-cyhalothrin to achieve efficient foliar delivery and insecticidal synergies

Nanocapsules are a promising controlled release formulation for foliar pest control. However, the complicated process and high cost limit widespread use in agriculture, so a simpler and more convenient preparation...