Rayaldee lipid-based formulation
Apr 3, 2021 20:43:27 GMT
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Post by Uncletlzz on Apr 3, 2021 20:43:27 GMT
Vitamin D obtained from sun exposure, foods, and supplements is biologically inert and must undergo two hydroxylations in the body for activation. The first hydroxylation, which occurs in the liver, converts vitamin D to 25-hydroxyvitamin D [25(OH)D], also known as “calcidiol.” The second hydroxylation occurs primarily in the kidney and forms the physiologically active 1,25-dihydroxyvitamin D [1,25(OH)2D], also known as “calcitriol”.
The delivery and absorption system is crucial.
When looking at Rayaldee in comparison to other marketed drugs and OTC alternatives, keep in mind that Rayaldee (the drug Calcifediol) is in a lipid-based formulation.
The development of LBFs was inspired by the phenomenon that a high-fat diet enhances the bioavailability of poorly water-soluble drugs.
Lipid-based formulations (LBFs) have demonstrated a great potential in enhancing the oral absorption of poorly water-soluble drugs.
Oral route is the most popular way for drug administration. Currently, more than 50% of marketed drugs and 90% of drug candidates are poorly water soluble, and these proportions continue to grow because of the rapid progress in drug discovery.
Great efforts have been made in the past to improve poor bioavailability of such compounds in an attempt to unlock their therapeutic potential as oral medicines and achieve some success
The enhancement of dissolution and absorption is one of the enduring research topics in pharmaceutical researches.
Rayaldee is s Biopharmaceutic classification system 2/4 with a Type of lipid-based formulation II/III.
Type II LBFs are self-emulsifying drug delivery systems (SEDDSs) comprising lipids and surfactants. The surfactants bear a hydrophilic–lipophilic balance (HLB) value of less than 12, and the type II LBFs generally form emulsions in aqueous media.
Type III LBFs consist of lipids, hydrophilic surfactants with a HLB value larger than 12, and hydrophilic cosolvents. They are subdivided into types IIIa (SEDDSs) and IIIb [self-microemulsifying DDSs (SMEDDSs) and self-nanoemulsifying DDSs (SNEDDSs)], based on the size of the formed emulsions.
Type II adds water-insoluble and dispersible surfactants to the oils, Type III incorporates water-soluble surfactants and hydrophilic cosolvents.
These formulations spontaneously self-emulsify upon contact with an aqueous environment.
Rayaldee is a Mixture of lipophilic emulsifier with a HLB <7 and an absorption enhancer with HLB of 13–18 Oily vehicle-mineral oil, liquid paraffins, or squalene.
Lipid-based drug delivery systems have become a technology of choice because they can enhance the oral bioavailability of drugs by increasing dissolution and solubility by pre-dissolving drugs in lipid carriers, improving drug permeability in the gastrointestinal tract (GI) by inhibition of P-gp and other efflux transporters, bypassing the first-pass metabolism of the drug through the lymphatic absorption processes.
There are other benefits to lipid-based drug delivery systems. For one, they have the potential to decrease the food-effect and increase reproducibility of the pharmacokinetic (PK) profile of orally administered drugs by reducing erratic absorption.
Lipid-based dosage forms bring the greatest benefits to lipophilic, insoluble drugs with poor bioavailability through GI absorption (BCS II) and a strong food effect. They can also improve the oral bioavailability of therapeutic entities, which are subject to efflux, high first-pass, low stability in GI fluids, or low permeability.
As a note on OTC Vitamin D and some approved standard analogs. A number of factors negotiate there absorption efficiency in human gastrointestinal tract.
These factors include variations in the physiochemical state of the vitamin D (molecular forms, potency and their physiological linkages), the complexity of food matrix (the amount and type of fatty acids, dietary fibers and presence/absence of vitamin D enhancer and inhibitor), and its interaction of other fat soluble compounds with vitamin D as well as the host-associated factors (age, disease, surgery, obesity, genetic variation etc.).
It is hypothesized that the bioavailability of vitamin D in the gastrointestinal tract is compromised if there are changes within these factors.
Certain medical problems, including Crohn's disease, cystic fibrosis, and celiac disease, can affect your intestine's ability to absorb vitamin D from the food you eat.
BMI (body mass index) higher than 30. Subcutaneous body fat can sequester, or trap, vitamin D, which is why deficiency is a greater concern in those who are obese.
Liver or kidney disease. Both diseases can negatively affect how your body processes vitamin D. Kidney disease may cause a person to have trouble processing vitamin D to its active form, calcitriol, which is used throughout the body. Some forms of liver disease cause problems with fat absorption, also making it harder to absorb vitamin D.
Radiation treatment. This type of cancer treatment can make it harder for the intestines to absorb vitamin D.
Weight loss surgery. These procedures reduce the size of the stomach or bypass part of the small intestine, thus making it harder for the body to consume adequate levels of many vitamins and minerals including vitamin D.
Some medications can also impact or inhibit vitamin D absorption, these include: Oral steroids, Orlistat, a weight-loss drug, Statins and Diuretics.
It is increasingly recognized that genetic factors influence serum 25(OH)D status.
Age-related changes affect vitamin D metabolism and increase the requirement for vitamin D in the elderly.
Rayaldee Calcifediol is more readily absorbed in the intestine than ergocalciferol or cholecalciferol due to its increased polarity and resulting lack of reliance on adequate bile secretion. The capsules gradually released calcifediol over a 12-hour period during in vitro dissolution testing.
Rayaldee (Modified-release (MR) calcifediol) gradually raises 25(OH)D3 and calcitriol. MR calcifediol effectively lowers iPTH without raising net vitamin catabolism.
Vitamins D2 and D3 (collectively “vitamin D”) are absorbed less readily than more polar vitamin D compound, and the degree of absorption can vary considerably between patients. Once absorbed, vitamin D must undergo two sequential hydroxylations to be active: first at carbon 25 by CYP2R1 or CYP27A1 to form 25-hydroxyvitamin D, and then at carbon 1 by CYP27B1 to form 1,25-dihydroxyvitamin D.
Rayaldee is more readily absorbed than vitamin D, and requires only 1-hydroxylation for activation with minimal CYP24A1 upregulation.
The delivery and absorption system is crucial.
When looking at Rayaldee in comparison to other marketed drugs and OTC alternatives, keep in mind that Rayaldee (the drug Calcifediol) is in a lipid-based formulation.
The development of LBFs was inspired by the phenomenon that a high-fat diet enhances the bioavailability of poorly water-soluble drugs.
Lipid-based formulations (LBFs) have demonstrated a great potential in enhancing the oral absorption of poorly water-soluble drugs.
Oral route is the most popular way for drug administration. Currently, more than 50% of marketed drugs and 90% of drug candidates are poorly water soluble, and these proportions continue to grow because of the rapid progress in drug discovery.
Great efforts have been made in the past to improve poor bioavailability of such compounds in an attempt to unlock their therapeutic potential as oral medicines and achieve some success
The enhancement of dissolution and absorption is one of the enduring research topics in pharmaceutical researches.
Rayaldee is s Biopharmaceutic classification system 2/4 with a Type of lipid-based formulation II/III.
Type II LBFs are self-emulsifying drug delivery systems (SEDDSs) comprising lipids and surfactants. The surfactants bear a hydrophilic–lipophilic balance (HLB) value of less than 12, and the type II LBFs generally form emulsions in aqueous media.
Type III LBFs consist of lipids, hydrophilic surfactants with a HLB value larger than 12, and hydrophilic cosolvents. They are subdivided into types IIIa (SEDDSs) and IIIb [self-microemulsifying DDSs (SMEDDSs) and self-nanoemulsifying DDSs (SNEDDSs)], based on the size of the formed emulsions.
Type II adds water-insoluble and dispersible surfactants to the oils, Type III incorporates water-soluble surfactants and hydrophilic cosolvents.
These formulations spontaneously self-emulsify upon contact with an aqueous environment.
Rayaldee is a Mixture of lipophilic emulsifier with a HLB <7 and an absorption enhancer with HLB of 13–18 Oily vehicle-mineral oil, liquid paraffins, or squalene.
Lipid-based drug delivery systems have become a technology of choice because they can enhance the oral bioavailability of drugs by increasing dissolution and solubility by pre-dissolving drugs in lipid carriers, improving drug permeability in the gastrointestinal tract (GI) by inhibition of P-gp and other efflux transporters, bypassing the first-pass metabolism of the drug through the lymphatic absorption processes.
There are other benefits to lipid-based drug delivery systems. For one, they have the potential to decrease the food-effect and increase reproducibility of the pharmacokinetic (PK) profile of orally administered drugs by reducing erratic absorption.
Lipid-based dosage forms bring the greatest benefits to lipophilic, insoluble drugs with poor bioavailability through GI absorption (BCS II) and a strong food effect. They can also improve the oral bioavailability of therapeutic entities, which are subject to efflux, high first-pass, low stability in GI fluids, or low permeability.
As a note on OTC Vitamin D and some approved standard analogs. A number of factors negotiate there absorption efficiency in human gastrointestinal tract.
These factors include variations in the physiochemical state of the vitamin D (molecular forms, potency and their physiological linkages), the complexity of food matrix (the amount and type of fatty acids, dietary fibers and presence/absence of vitamin D enhancer and inhibitor), and its interaction of other fat soluble compounds with vitamin D as well as the host-associated factors (age, disease, surgery, obesity, genetic variation etc.).
It is hypothesized that the bioavailability of vitamin D in the gastrointestinal tract is compromised if there are changes within these factors.
Certain medical problems, including Crohn's disease, cystic fibrosis, and celiac disease, can affect your intestine's ability to absorb vitamin D from the food you eat.
BMI (body mass index) higher than 30. Subcutaneous body fat can sequester, or trap, vitamin D, which is why deficiency is a greater concern in those who are obese.
Liver or kidney disease. Both diseases can negatively affect how your body processes vitamin D. Kidney disease may cause a person to have trouble processing vitamin D to its active form, calcitriol, which is used throughout the body. Some forms of liver disease cause problems with fat absorption, also making it harder to absorb vitamin D.
Radiation treatment. This type of cancer treatment can make it harder for the intestines to absorb vitamin D.
Weight loss surgery. These procedures reduce the size of the stomach or bypass part of the small intestine, thus making it harder for the body to consume adequate levels of many vitamins and minerals including vitamin D.
Some medications can also impact or inhibit vitamin D absorption, these include: Oral steroids, Orlistat, a weight-loss drug, Statins and Diuretics.
It is increasingly recognized that genetic factors influence serum 25(OH)D status.
Age-related changes affect vitamin D metabolism and increase the requirement for vitamin D in the elderly.
Rayaldee Calcifediol is more readily absorbed in the intestine than ergocalciferol or cholecalciferol due to its increased polarity and resulting lack of reliance on adequate bile secretion. The capsules gradually released calcifediol over a 12-hour period during in vitro dissolution testing.
Rayaldee (Modified-release (MR) calcifediol) gradually raises 25(OH)D3 and calcitriol. MR calcifediol effectively lowers iPTH without raising net vitamin catabolism.
Vitamins D2 and D3 (collectively “vitamin D”) are absorbed less readily than more polar vitamin D compound, and the degree of absorption can vary considerably between patients. Once absorbed, vitamin D must undergo two sequential hydroxylations to be active: first at carbon 25 by CYP2R1 or CYP27A1 to form 25-hydroxyvitamin D, and then at carbon 1 by CYP27B1 to form 1,25-dihydroxyvitamin D.
Rayaldee is more readily absorbed than vitamin D, and requires only 1-hydroxylation for activation with minimal CYP24A1 upregulation.