Wp Formulation
Avenall Trejo
Formulation is a term used in various senses in various applications, both the material and the abstract or formal. Its fundamental meaning is the putting together of components in appropriate relationships or structures, according to a formula. Etymologically formula is the diminutive of the Latin forma, meaning shape. In that sense a formulation is created according to the standard for the product.[1]
Disciplines in which one might use the word formulation in the abstract sense include logic, mathematics, linguistics, legal theory, and computer science. For details, see the related articles.
In more material senses the concept of formulation appears in the physical sciences, such as physics, chemistry, and biology. It also is ubiquitous in industry, engineering and medicine, especially pharmaceutics.
In pharmacy, a formulation is a mixture or a structure such as a capsule, tablet, or an emulsion, prepared according to a specific procedure (called a "formula"). Formulations are a very important aspect of creating medicines, since they are essential to ensuring that the active part of the drug is delivered to the correct part of the body, in the right concentration, and at the right rate (not too fast and not too slowly). A good example is a drug delivery system that exploits supersaturation. They also need to have an acceptable taste (in the case of pills, tablets or syrups), last long enough in storage still to be safe and effective when used, and be sufficiently stable both physically and chemically to be transported from where they are manufactured to the eventual consumer. Competently designed formulations for particular applications are safer, more effective, and more economical than any of their components used singly.
Some components impart specific properties to the formulation when it is put into use. For example, certain components (polymers) are used in paint formulations to achieve deforming or levelling properties.[2] Some components of a formulation may only be active in particular applications.
The National Indian Health Board (NIHB) provides unique insights into the needs of Indian health system during the annual federal budget formulation cycle. The NIHB provides technical support the Indian Health Service (IHS) Tribal Budget Workgroup, which makes recommendations to the Indian Health Service on Tribal budget priorities. Every year, the Workgroup diligently works to synthesize the priorities identified by the Tribes in each of the 12 IHS Areas into a cohesive message outlining Tribal funding priorities nationally.
PFGs support project formulation activities, including among others feasibility studies or consultations. A PFG could only be awarded if it is presented along with a project pre-concept or project concept presented to and endorsed by the Board.
Since the forty-second meeting of the Adaptation Fund Board (AFB42) held in April 2024, PFGs are now available for all IEs. All accredited IEs of the Fund are eligible to apply for PFG grants. The PFG grant should be requested at the same time when IEs going through the two-step approval process submits project concepts or the three-step approval process to submit project pre-concepts for regional proposals.
Robust early phase development programs
Comprehensive preformulation testing#ctl-banner--formulation---865115634087022191 .content * color: #FFFFFF;FORMULATIONOur proven data-driven approaches speed drug candidates into first-in-man studies, then quickly advance them to formulated products. Our small molecule drug development capabilities and expertise can help overcome solubility challenges, optimize your API, improve timelines and help advance your molecule to clinic.
Following the resolution at the 69th World Health Assembly on promoting innovation and access to quality, safe, efficacious and affordable medicines for children, GAP-f was conceived to build on and formalize the model developed within the HIV community to provide a sustainable mechanism that ensures that safer, more effective, and more durable paediatric formulations are developed and made available to children against an accelerated timeline.
At GAP-f, Children are at the top of our agenda. While there have been significant achievements in child health with six million fewer children under the age of five years dying in 2016 than in 1990, urgent action is needed to achieve the UN Sustainable Development Goals (SDG), particularly SDG 3, which aims to ensure healthy lives and promote wellbeing for all people at all ages and the related target to achieve Universal Health Coverage by 2030.
Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.
Injectable insulin is an extensively used medication with potential life-threatening hypoglycaemic events. Here we report on insulin-conjugated silver sulfide quantum dots coated with a chitosan/glucose polymer to produce a responsive oral insulin nanoformulation. This formulation is pH responsive, is insoluble in acidic environments and shows increased absorption in human duodenum explants and Caenorhabditis elegans at neutral pH. The formulation is sensitive to glucosidase enzymes to trigger insulin release. It is found that the formulation distributes to the liver in mice and rats after oral administration and promotes a dose-dependent reduction in blood glucose without promoting hypoglycaemia or weight gain in diabetic rodents. Non-diabetic baboons also show a dose-dependent reduction in blood glucose. No biochemical or haematological toxicity or adverse events were observed in mice, rats and non-human primates. The formulation demonstrates the potential to orally control blood glucose without hypoglycaemic episodes.
The escalating disease burden of diabetes mellitus, with a global prevalence of 425 million people, is a critical health priority with multifaceted demands for patients, carers, health systems and the economy1. Of this population, 75 million are insulin dependent1,2. These severe insulin-deficient and insulin-resistant subtypes require strict glycaemic control via a combination of injectable or infusions of insulin, lifestyle interventions and continuous glucose monitoring to reduce the incidence of acute adverse events (hyperglycaemia and hypoglycaemia) and the development of long-term complications such as cardiovascular disease3 or nephro-, neuro- and retinopathies4,5,6,7.
Of these complications, hypoglycaemia is a dangerous side effect of insulin treatment8, correlating with reduced health-related quality of life and productivity and increased health-care resource utilization9,10,11. In 2020, the economic cost of type 1 diabetes (T1D) alone was 2.9 billion USD, with 60% due to indirect costs (patient well-being and productivity)12,13. Reduction in hypoglycaemic events without the loss of glycaemic control is critical to improve patient well-being14 and reduce the risk of cardiovascular disease and mortality8. In light of these costs and existing injectable insulin complications, there is a need to examine alternative methods of insulin delivery to redesign insulin to end hypoglycaemic risk15. These technologies must also be cost-effective given the recent evidence that insulin pump management is not a health economic cost-saving measure compared with user education16.
QD-INS was insoluble with reduced optical density and transmission between pH 3.5 and pH 6.5 (Extended Data Fig. 1). Given that the isoelectric point of Ag2S QDs and insulin were 2.8 and 5.3, respectively, we investigated the changes in zeta (ζ)-potential of QD-INS. Between pH 3 and pH 6, the ζ-potential demonstrated a near-zero value, suggesting a broad range over which QD-INS maintained a net neutral charge leading to poor colloidal stability and precipitate formation (Extended Data Fig. 1).
The chemical structure of CS/GS was determined by one-dimensional 1H and two-dimensional [1H,1H] nuclear Overhauser effect spectroscopy (NOESY), NMR and FTIR (Fig. 1b and Extended Data Figs. 2, 4 and 5). The prominence of β-1,4 glycosidic bonds in FTIR was due to the use of deacetylated chitosan (glucosamine monomers) that polymerize via these β-1,4 glycosidic bonds. Glucose monomers typically form α-1,4 or α-1,6 glycosidic bonds when forming glycogen or starch; however, in a long chain, they can also form β-1,4 glycosidic bonds to form cellulose33. CS/GS appears to contain both α and β glycosidic bonds and was designed to be susceptible to this form of degradation, with breakdown leading to the release of insulin.
Increasing the concentration of CS/GS led to a corresponding increase in the HD diameter (Fig. 1f). Interestingly, CS/GS-concentration-dependent effects on HD diameter were also influenced by pH, with low pH increasing the HD diameter and vice versa (Fig. 1f). This effect is probably related to the pH-dependent insolubility and agglomeration of particles (Extended Data Fig. 1). Initial insulin tolerance testing (ITT) in mice demonstrated that the polymer coating was required to reduce blood glucose (BG), highlighting a critical size requirement for efficacy (Fig. 1g).
The main finding from this study is the absence of hypoglycaemia observed in mice, rats and baboons. A key aspect of utilizing glucosidase-responsive materials is that these enzymes facilitate saccharide/glycoside/fructose breakdown41,42,47, critical roles involved in post-food intake and correlated with glycolytic activity55. Recently, it was demonstrated that the β-glucosidase chemical activity directly correlates with glucose concentrations56. Together, this suggests that the degradation rate of CS/GS may depend on the glucose/saccharide concentration. Specific hepatic targeting of insulin may also be key to the reduced episodes of hypoglycaemia and reduce the adverse effects of hyperinsulinaemia compared with parenteral administration of animals such as weight gain and insulin resistance29,57.
c80f0f1006