What are LNP nanoparticles?
Lipid nanoparticle (LNP) is a lipid vesicle with a uniform lipid core, usually around 100 nm in diameter. This unique structure and size give it unique physical and chemical properties, which can effectively encapsulate and protect nucleic acid drugs, such as mRNA, siRNA, antisense oligonucleotides, etc., to be transported to the target tissue or cell through the blood circulation system.
What is the composition of lipid nanoparticles?
Cholesterol: contributes to membrane stability and fluidity, affects particle cycle time and structural integrity.
Phospholipids: such as lecithin, used to form lipid bilayer, improve the stability and biocompatibility of the preparation.
Ionizable/cationic lipids: Protonated at low pH, positively charged, but neutral at physiological pH, conducive to nucleic acid delivery.
Pegylated lipids: Incorporated into the outer layer of the particle to improve stability and cycle time and reduce immune recognition.
What is solid lipid nanoparticles?
Solid lipid nanoparticles (SLNS) are the first generation of lipid nanoparticles, formed by solid natural or synthetic lipids coated with drugs to form a solid glial drug delivery system. Solid lipid nanoparticles are derived from O/W emulsions, which replace the liquid lipid of the emulsion with a lipid matrix, and become solid at body temperature, and are stabilized by surfactants.
Can lipid nanoparticles cross the blood brain barrier?
LNPs have the potential to cross the blood-brain barrier (BBB). The blood-brain barrier is a protective mechanism whose primary function is to prevent potentially harmful substances from entering the brain. However, this also makes it difficult for many therapeutic drugs to reach the central nervous system.
LNPs may cross the blood-brain barrier through the following mechanisms:
Passive diffusion: Some small-sized LNPs can diffuse through tight junctions of BBBS.
Endocytosis: Some modified LNPs can be actively absorbed by brain capillary endothelial cells through the endocytosis pathway and then released into brain tissue.
Adsorptive-mediated transport: By modifying the surface charge or chemical group of the nanoparticle, it enhances its interaction with the cell membrane, thereby facilitating its crossing of the BBB.
Receptor-mediated transport: By modifying specific ligands on the LNP surface to bind to corresponding receptors on BBB to facilitate crossing.
How does the size of lipid nanoparticles affect their properties?
Particle size is an important factor affecting the physical stability, solubility, dissolution rate, bioavailability and targeting of lipid nanoparticles. Smaller particles typically have a higher surface-area-to-volume ratio, resulting in higher solubility and faster dissolution rates. However, smaller particles may also have a higher tendency to aggregate and a lower loading capacity.
What is the meaning of zeta potential of lipid nanoparticles?
Zeta potential represents the surface charge of lipid nanoparticles in liquid media, which affects the colloidal stability, aggregation behavior, flocculation rate and interaction with biofilm. A higher zeta potential usually implies higher electrostatic repulsion and better stability, but may also increase the toxicity and immunogenicity of lipid nanoparticles. ZP values above +30 mv or below -30 mv are sufficient to repel each other and maintain electrostatic stability.
What are the preparation methods of lipid nanoparticles?
High pressure homogenization method: By mixing the lipid solution and the drug solution and undergoing high pressure treatment, the solution forms uniform nanoparticles. This method is suitable for mass production.
Solvent volatilization: The lipids and drugs are dissolved in a solvent, and then the lipids self-assemble into nanoparticles by evaporating the solvent.
Thin film water method: lipid nanoparticles are formed by dissolving the lipid into a film and hydrating in an aqueous solution.
Ultrasonic method: Through the action of ultrasound, lipid molecules and drug molecules are fused to form nanoparticles.
The choice of these methods directly affects key parameters such as particle size, polydispersion index, zeta potential and drug capture rate.
How to regulate the properties of lipid nanoparticles?
The properties of lipid nanoparticles (such as size, surface charge, drug load, etc.) can be regulated by a variety of means:
Lipid composition: Changing the ratio of different lipids (such as cationic lipids, anionic lipids, and neutral lipids) can affect particle stability and surface charge.
Surface modification: By introducing polyethylene glycol (PEG) or other targeted molecules on the surface of lipid nanoparticles, the biological distribution of the particles can be improved and clearance by the immune system can be reduced.
Drug/lipid ratio: The ratio of drugs to lipids directly affects the encapsulation efficiency of drugs and the stability of lipid particles, and a reasonable drug/lipid ratio helps to improve the efficiency of drug loading and delivery.
What are the important parameters for the characterization of lipid nanoparticles?
The key characterization parameters of lipid nanoparticles include particle size, surface charge (Zeta potential), drug loading, drug release rate and stability. The particle size had important effects on the biological distribution and cellular uptake of LNPs. Zeta potential affects the stability and interaction of particles. The drug loading and the rate of drug release directly affect the curative effect.
What methods are available to characterize lipid nanoparticles?
Dynamic light scattering (DLS): Commonly used to measure particle size and Zeta potential. The average particle size of LNPS is typically between 100-400 nm, with an ideal range of 10-150 nm for intravenous drug delivery.
Nanoparticle size analyzer: The size and distribution of particles can be analyzed more precisely by light scattering or ultrasonic techniques.
Transmission electron microscopy (TEM) : TEM can provide morphological characteristics of particles and can be used to observe the size and shape of individual particles.
Scanning electron microscopy (SEM): Similar to TEM, SEM can provide surface morphological characteristics of particles, which is especially suitable for the analysis of surface structure.
Atomic force microscopy (AFM): AFM provides a three-dimensional topography of particles and is used to measure their surface roughness and height.
High performance liquid chromatography (HPLC): Used to analyze and determine drug content in LNPs.
Differential scanning calorimetry (DSC): Used to detect the thermal stability and crystal changes of lipids.
How to evaluate the stability of lipid nanoparticles?
The stability of LNPs can be evaluated by particle size change, Zeta potential, and drug release characteristics during storage. Storage stability tests are often performed at different temperatures, pH, and ionic strengths to simulate the in vivo and in vitro environment.
Are lipid nanoparticles safe for humans?
Lipid nanoparticles (LNPs) are generally considered safe for use in humans and are widely used as delivery systems for drugs, including vaccines. The safety of lipid nanoparticles depends on several factors, including their composition, size, surface charge, and the route of administration. Here are some points to consider regarding their safety:
Biocompatibility: LNPs are designed to be biocompatible and biodegradable, meaning they can be safely absorbed or broken down by the body.
Adverse reactions: Like any medical intervention, LNPs can cause adverse reactions in some individuals. These reactions are usually mild and temporary, such as injection site pain or mild fever. Severe reactions are rare.
Clinical testing: Before approval, any LNP-based drug or vaccine undergoes rigorous clinical testing to assess its safety and efficacy. Regulatory agencies like the FDA or EMA evaluate the data to ensure safety standards are met.
Ongoing research: Research continues to optimize LNP formulations for increasing safety and efficacy, minimizing potential side effects, and targeting specific cells or tissues more effectively.
How to evaluate the safety and toxicity of lipid nanoparticles?
The safety evaluation of lipid nanoparticles is an important step in drug development. The assessment mainly includes:
Evaluation of acute and chronic toxicity: The toxicity of LNPs was evaluated through animal experiments, including acute toxicity and effects after long-term use.
Immune response: Since lipid nanoparticles may trigger immune responses, especially immune activation problems associated with PEG trimmers, immunotoxicity studies are needed.
Biocompatibility test: The components of LNPs usually have good biocompatibility, but the ratio, dosage and use of different components may have different reactions to organisms, so detailed biosafety assessment is required.
What is the function of the lipids in the LNPs?
The selection and optimization of lipids in LNP is directly related to the success of drug delivery.
Lipids constitute the main structure of the LNP and form closed particles through self-assembly, thus wrapping and protecting the internal drug molecules, such as mRNA or siRNA, from degradation by the external environment. The lipid layer is able to improve the stability of the drug, giving it a longer half-life in the body. Modified lipids on the surface of LNP can be used to target specific cells or tissues, improving delivery efficiency. Different lipid components can regulate the particle size, charge and surface properties of LNP, and then affect its distribution in vivo and cellular uptake pathway. Some cationic lipids can form complexes with nucleic acids, improving the ability of nucleic acids to cross cell membranes and ensuring the effective release of drugs within the cell.
What are the applications of lipid nanoparticles?
Vaccine development: LNs is used in the formulation of mRNA vaccines to promote a highly effective immune response.
mRNA therapy: LNs can target and control the delivery of mRNA, which is suitable for the treatment of a variety of diseases.
Gene delivery: Improve the efficiency of gene delivery, opening up new possibilities for gene editing and personalized medicine.
What is the difference between liposomes and LNP?
Both liposomes and LNPs are vectors used to deliver drugs and genetic material, but there are some differences in their structure and use. Liposomes are spherical vesicles surrounded by a phospholipid bilayer that can enclose both hydrophilic and hydrophobic (such as hydrophobic drugs) components, and are more similar in structure to cell membranes, so they are often used for drug delivery. In contrast, LNPs are more complex structures, usually composed of lipids, cholesterol, polyethylene glycol derivatives, and other components, and thus exhibit better stability and distribution characteristics in vivo. LNPs are mainly used for nucleic acid delivery such as mRNA vaccines.
What is the role of lipid nanoparticles in mRNA vaccines?
Lipid nanoparticles play a key delivery and protection role in mRNA vaccines. mRNA itself is easily degraded, and lipid nanoparticles can protect mRNA from the degradation of nuclease in the body, and promote its efficient transfer to the cell to achieve expression. Ionized lipids in LNP can form complexes with mRNA, while PEG-lipids improve particle stability and half-life.
What are the applications of lipid nanoparticles in different drug delivery routes?
Lipid nanoparticles are suitable for a variety of drug delivery routes, including oral, intravenous, and local administration. They enable targeted delivery and release of drugs through different mechanisms, thereby improving therapeutic effectiveness and reducing side effects.
What are the specific mechanisms by which lipid nanoparticles improve drug bioavailability?
The specific mechanism of LNP in improving drug bioavailability mainly includes the following aspects:
Enhanced solubility and absorption of drugs: Lipid nanoparticles increase the solubility of drugs by increasing their specific surface area. According to the Noyes-Whitney dissolution formula, the smaller the volume of drug particles, the larger the specific surface area and the better the solubility. In addition, lipid nanoparticles can improve the affinity and permeability of the drug to the gastrointestinal mucosa, thereby improving the bioavailability of oral drugs.
Control drug release: Lipid nanoparticles can achieve the slow controlled release of drugs and extend the circulation time of drugs in the body. For example, by adjusting the lipid composition ratio, the formation of lipid-mrna adduct can be reduced, ensuring mRNA translation and protein expression. This ability to control release helps improve treatment effectiveness and reduce side effects.
Targeted delivery: Lipid nanoparticles can be surface modified to achieve targeted delivery to specific cells or tissues. For example, surface functionalization using ligands such as antibodies, proteins, and aptamers can enable targeting of specific cell types. This not only improves the targeting of the drug, but also reduces non-targeted effects and systemic toxicity.
Enhanced cell uptake: Due to the similar physical properties of lipids and cell membranes, lipid nanoparticles have stronger adhesion to cell membranes and can enhance cell uptake of drugs. In addition, when the nanoparticles are attracted to the cell membrane by electrostatic forces, adsorption occurs and ultimately promotes the release of internal materials.
Improved drug stability: Lipid nanoparticles can protect encapsulated drugs from external environmental influences such as nuclease-mediated degradation and strong immune responses. This is of great significance for improving the stability and prolonging the half-life of the drug.
What are the surface modification techniques for lipid nanoparticles and how do they affect their delivery efficiency and safety?
The surface modification technology of LNP is an important means to improve its delivery efficiency and safety. The following are several common surface modification techniques:
PEG modification: PEG (polyethylene glycol) modification reduces immune system recognition and clearance by forming a hydrophilic protective layer on the surface of lipid nanoparticles, extending blood circulation time. This modification can inhibit aggregation and non-specific interactions, thereby improving drug stability and targeting.
MH42 modification: MH42 modification significantly enhances its targeting and cellular uptake of specific cell types by attaching specific MH42 molecules to the surface of lipid nanoparticles. This modification improves the affinity of lipid nanoparticles to immune cells, thus effectively improving the delivery efficiency of mRNA vaccines and gene therapy drugs.
Antibody modification: By attaching specific antibodies to the surface of lipid nanoparticles, these nanoparticles can specifically recognize and bind to cells expressing specific antigens, improving the targeting and cell uptake ability of lipid nanoparticles, and helping to improve the efficacy and safety of drugs. For example, lipid nanoparticles modified with PECAM-1 specific antibodies are able to specifically recognize and bind to cells that express PECAM-1, such as endothelial cells.
Nucleic acid modification: By modifying nucleic acids such as microRNA or siRNA to the surface of lipid nanoparticles, it can enhance their stability and translation efficiency, reduce the immune response in vivo, and improve the safety and effectiveness of gene expression.
Environmental response group modification: By introducing environmental response groups, lipid nanoparticles can undergo structural changes under specific conditions, such as pH changes, enabling controlled release of drugs.
Fluorescence modification: By introducing fluorophores on the surface of lipid nanoparticles, fluorescence modification allows real-time monitoring of their distribution and delivery process in the body. It is helpful to study the delivery path and targeting effect of lipid nanoparticles, so as to optimize their design.
What is ADME? What is the role of ADME?
ADME is short for drug absorption, distribution, metabolism and excretion, representing the body's disposal process of drugs. The ADME properties of a drug are determined by its structure, and measuring the ADME properties of a drug can provide an important reference value for predicting its bioavailability and bioactivity (that is, whether a drug can reach its target and produce the corresponding therapeutic effect). In the drug discovery phase, ADME testing is used to screen suitable drug candidates for marketing, avoiding wasting resources in expensive in vivo testing. During the drug optimization phase, ADME screening determines the pharmacokinetic properties of the compounds, ensuring good oral bioavailability and plasma clearance. In the clinical trial phase, ADME studies monitor the absorption, distribution, metabolism, and excretion of radioisotopically labeled drugs in the human body by administering a single dose to healthy volunteers to assess the safety and efficacy of the drugs.
How to run ADME tests?
ADME testing usually includes both in vitro and in vivo methods. In vitro tests such as Caco-2 cell permeability assay, microsomal/hepatocyte stability assay, CYP450 inhibition assay, etc. are used to predict drug absorption, metabolism, and excretion characteristics. In vivo testing provides quantitative information on the distribution, metabolism and excretion of drugs and their metabolites in the body through the use of radiolabels.
What is the difference between pharmacokinetics and ADME?
Pharmacokinetics (PK) and ADME are two concepts closely related to the behavior of drugs in the human body. Pharmacokinetics mainly focuses on the law of drug concentration changes in the body over time, including drug Absorption, Distribution, Metabolism and Excretion (ADME process). Together, these four processes determine the level and duration of drug exposure in the body. ADME, on the other hand, is part of pharmacokinetics, which focuses on describing the specific paths and ways of drugs in the body.
What is in vitro ADME testing?
In vitro ADME testing refers to the use of experimental models such as cell lines, microsomes, and liver slices to evaluate the absorption, distribution, metabolism and excretion processes of drugs in a laboratory environment. This test method does not rely on living animals, can provide preliminary drug behavior data for drug development, and has a low ethical burden and cost.
Can we only rely on in vitro testing to understand the ADME properties of a drug, and why do we need in vivo testing?
In vitro testing can provide information on the basic physico-chemical properties of drugs, such as solubility and cell membrane permeability, but cannot fully simulate the in vivo environment, such as complex processes such as blood circulation, liver metabolism, and protein binding. Therefore, in vivo experiments, often conducted in animal models, are necessary to accurately reflect the systemic distribution, metabolic pathways, and excretion of the drug, and to verify the results of in vitro experiments. Combined in vivo and in vitro testing can be used to evaluate the ADME properties of drugs more comprehensively.
How to improve drug absorption for API with low absorption rate?
Drug absorption rate is affected by many factors, including solubility, molecular size, charge and cell membrane affinity. Ways to improve the low absorption rate are:
Optimization of molecular structure: Adjustment of lipophilicity or chemical modification to enhance biofilm penetration.
Use of cosolvents or surfactants: Excipients are added to enhance drug solubility and promote gastrointestinal absorption.
Development of sustained-release or nano formulations: Increase absorption efficiency by extending drug retention time.
Improved dosage forms: such as conversion into soft capsules or nanoparticles to increase solubility and bioavailability.
How does the metabolic pathway of a drug affect ADME test results?
Drug metabolism pathway has important influence on its ADME characteristics. Drugs are metabolized in the body primarily by enzymes in the liver, such as the CYP450 family, producing active or inactive metabolites. The metabolic rate and the properties of the metabolites will directly affect the safety and efficacy of the drug. Rapid metabolism may lead to insufficient blood drug concentration, while too slow metabolism may cause drug accumulation and toxic reactions.
ADME tests reveal the metabolic pathways of drugs and their metabolites and assess the impact of these factors on drug safety and efficacy. If adverse metabolites or potential drug interactions are detected, these problems can be mitigated by adjusting the molecular structure or changing the dosage form.
What is bioavailability? How is bioavailability of drugs assessed?
Bioavailability (BA) is defined as the proportion of drugs that enter the systemic circulation and can be used by the body. It depends on the solubility, absorption efficiency and metabolic pathway of the drug. In ADME testing, bioavailability is usually assessed by comparing the concentration time curve of the drug in plasma after oral administration and intravenous administration. If oral administration has low bioavailability, it may be necessary to optimize the dosage form or add excipients to improve absorption.
The evaluation of bioavailability is critical to understanding the effectiveness and pharmacokinetic properties of drugs and helps determine the best route of administration and dosage form design.
What is the purpose of toxicology testing?
Toxicology testing is designed to assess the safety of the drug, including determining a safe dose range, identifying side effects, and assessing safety concerns for long-term or repeated use of the drug. The tests cover acute, chronic, genetic, immune, and cardiotoxicity to predict potential safety issues in clinical trials, guide clinical trial design, and reduce the risk of uncertainty in the development process.
What are the common types of toxicology tests?
Acute toxicity testing: evaluates the acute adverse reactions that may be caused after a single dose, usually quantifying the acute risk of a drug by determining a lethal dose, such as LD50.
Chronic toxicity tests: Evaluate safety after long-term or repeated administration to detect potential chronic disease, organ damage, or carcinogenicity. This type of testing involves prolonged animal trials, where the drug is administered for months to years.
Genotoxicity tests: Assess the likelihood that a drug will cause genetic mutations, chromosome damage, or other genetic changes. Common test methods include AMES test and micronucleus test.
Immunotoxicity test: Evaluate the effect of a drug on the immune system and identify whether it causes immunosuppression or immune overreaction.
Reproductive toxicity tests: Assess the effects of drugs on the reproductive system and fetal development, including the ability to conceive, fetal growth and birth defects.
Cardiotoxicity testing: evaluates the effects of a drug on cardiac function, specifically cardiac electrophysiological properties (such as hERG channel activity) to predict cardiac safety.
What are toxicology testing procedures?
Preliminary screening: Early in drug development, acute toxicity testing and in vitro toxicity assessment (e.g. cytotoxicity assay) are performed to identify potential toxicity. At this stage, in vitro models or small-scale animal experiments are used to initially understand the safety of the drug.
Dose-determination and animal testing: Based on preliminary results, further toxicity studies are conducted, including chronic, genetic, and immunotoxicity tests. Using rodent models, different dose groups were set up to evaluate lethal dose, organ effects, and metabolic stability.
Long-term safety assessment: For drugs that have shown a good safety profile, long-term exposure testing is performed to assess whether long-term use of drugs will lead to the accumulation of toxicity or chronic adverse reactions. Such tests typically last six months or more and monitor the long-term effects of the drug.
Each stage is progressively advanced to provide comprehensive data support for the safety of the drug and ensure the safety and effectiveness of its clinical application.
Based on the characteristics of the drug, how to choose the appropriate toxicology test method? Does every drug need to be tested for all types of toxicology?
The choice of an appropriate toxicological test depends on the nature of the drug, route of administration, dosage, and intended clinical application. For example:
Small molecule drugs: For traditional small molecule drugs, basic tests such as acute toxicity, chronic toxicity, genetic toxicity and organ toxicity are usually required. If the drug is expected to be used for a long period of time, evaluation of chronic toxicity, immunotoxicity, and reproductive toxicity may be required.
Biopharmaceuticals (such as antibody drugs, protein drugs): Because of their specificity, biopharmaceuticals may need to pay more attention to issues such as immunotoxicity, antibody specificity, and biodegradability. For biopharmaceuticals, toxicity testing related to the immune system is also required to ensure that it does not cause an excessive immune response.
Special drugs (such as nanomedical drugs, gene therapy drugs, etc.): Toxicological testing of such drugs requires special attention to the specific toxicity of the drug, including the biocompatibility of nanoparticles, and the genomic safety of gene therapy.
Not every drug requires all types of toxicology testing, but core acute and chronic toxicity, genotoxicity testing is a must for almost every drug. The specific test program is usually adjusted based on the characteristics of the drug and the design of the clinical trial.
What if the toxicology test results are not good?
If the toxicology test results are not satisfactory, the research and development team needs to first analyze the nature and mechanism of the toxic reaction to determine whether it is caused by the molecular structure of the drug, the high dose, or some specific drug formulation. Treatment options may include:
Optimization of molecular structure: Based on the results of toxicity tests, the chemical structure of the drug is adjusted to reduce the risk of adverse reactions. For example, modifying certain chemical groups of drug molecules or improving their metabolic pathways reduces the production of toxic substances.
Dose adjustment: If tests show toxic reactions at high doses, consider lowering the dose in the clinical trial and performing dose-response curve analysis to find a safe and effective dose range.
Improved dosage form or route of administration: By changing the route of administration of the drug (for example, oral instead of topical administration or injection) or adjusting the mode of release of the drug, the toxic effects of the drug on certain organs can be reduced.
Termination of development: If the toxicity problem cannot be effectively addressed by adjusting the structure, dosage form or dosage, it may be necessary to consider terminating the development of the drug, especially if the toxicity problem is severely irreversible.
Do you offer high throughput ADME screening services?
LC-MS/MS method optimization and data processing: Our high-throughput ADME screening services include MS/MS method optimization, ADME detection, sample removal, LC-MS/MS raw data collection and processing, and archiving of post-analysis data. These steps ensure the accuracy and reliability of high-throughput screening.
Virtual screening methods: Virtual screening methods are considered as alternative methods to predict the properties of candidate compounds ADME, with high or ultra-high throughput characteristics. This approach facilitates Hit extension and structure-activity relationship construction through cheminformatics, molecular modeling, and iterative access to the field compound library.
What is capsule in pharmacy?
Capsules are solid preparations made by filling the drug or suitable excipients in hollow hard capsules or sealed in soft capsules.
What is soft gel?
Soft gel capsule refers to a certain amount of liquid drug directly enveloped, or solid drug dissolved or dispersed in a suitable excipient prepared into a solution, suspension, emulsion or semi-solid, sealed in the soft capsule material made of capsules.
What are the main differences between softgel and tablet?
Softgel capsule refers to a certain amount of drugs dissolved in appropriate excipients, and then sealed in a spherical or oval soft capsule by pressing or dropping method. When made by pressing, there is often a nip in the middle; when made by dripping, it is spherical and seamless. Softgel capsules can generally be swallowed as a whole, or the capsule can be cut and squeezed out to take the drug directly, such as vitamin D3 soft capsules. In contrast, tablets are solid dosage forms formed by pressing solid particles, such as powders or fine particles, and often require the addition of excipients such as adhesives and fillers to ensure their structural stability.
In terms of dissolution properties, softgel usually dissolves quickly in the gastrointestinal environment, which is suitable for the rapid release of drugs. The dissolution rate of tablets depends on their specific formulation, and may exhibit a slower dissolution rate for insoluble drugs. In addition, softgel capsules, due to their shape and texture, are generally easier to swallow and especially more friendly to children and the elderly, thus improving patient medication compliance. Conversely, tablets may affect patient acceptance because of size, taste, or difficulty swallowing.
Are soft gel vitamins better than tablets?
Some vitamins and nutrients, especially fat-soluble ones like vitamins A, D, E, and K, might be better suited for soft gels.
What are pill capsules made of? What's the difference between softgel capsules and hard capsules?
Softgel capsules are made of thin and flexible gelatin or similar materials and are suitable for encapsulating liquid or semi-solid medicines such as vitamins and plant extracts. Hard capsule preparation refers to a certain amount of drugs and appropriate excipients made of uniform powder or particles, filled in hollow hard capsules. The capsule shell uses a relatively strong gelatin material, and although the capsule shell itself is not effective, it plays an important role. First, the capsule shell of a hard capsule preparation can avoid burning the esophagus with the drug, such as minocycline capsules. It can also avoid irritation of the stomach or protect the drug from being destroyed by stomach acid, such as enteric capsules. Secondly, extend the time of drug action and control the speed of drug release, such as slow-controlled release capsules. Chinese medicine capsules can also cover up the bad smell of medicine. If the capsule is taken apart, it may reduce the efficacy or increase the adverse stimulation of the drug, which is not conducive to the accurate grasp of the drug dose. Therefore, it is generally not appropriate to take the capsule apart.
How are soft gel capsules made?
Soft gel capsules are made using a specialized encapsulation process that involves several key steps.
Preparation of the gelatin mixture: The outer shell of soft gel capsules is usually made from gelatin. The gelatin is mixed with water and a plasticizer such as glycerin or sorbitol to give it the desired flexibility and strength. This mixture is heated and thoroughly blended until it's homogeneous.
Formulation of the fill material: The active ingredients, along with any excipients, are dissolved or suspended in a liquid to create the fill material. This liquid can be an oil or another hydrophobic carrier that is compatible with the gelatin shell.
Encapsulation: The most common method for creating softgels is called the rotary die process. This involves feeding the gelatin and the fill material into a machine where two rotary dies come together. The gelatin forms a ribbon that is continuously fed onto the rotating die, allowing capsules to be formed in the desired size and shape as the fill material is simultaneously injected.
Sealing and trimming: As the gelatin encapsulates the fill material, it's sealed by the pressure and heat applied by the rotary dies. The excess gelatin is trimmed away, leaving the sealed capsule.
Tumbling and drying: Newly formed softgels are sticky, so they go through a tumbling process to prevent them from adhering to each other. They are then left to dry in a controlled environment, allowing the gelatin to set and harden to its final state.
Inspection and quality control: The softgels are inspected for uniformity, fill weight accuracy, and any defects. They may undergo additional quality testing for content uniformity and potential contaminants.
Packaging: Once they pass quality control, the soft gel capsules are bottled or blister-packed for distribution.
What are softgels used for?
Softgel capsules usually require animal and vegetable oils or liquid fillers as the main ingredient, so when selecting API (active pharmaceutical ingredient), it will be more appropriate to choose those ingredients that have good solubility in the oil. The following are some types of APIs that are commonly applicable to softgel preparations:
Oil-soluble API, such as OMEGA-3 fatty acids, curcumin, coenzyme Q10, evening primrose oil and other plant extracts.
Strong smell or bitter API.
APIs that are susceptible to moisture or oxidation can be protected from the outside environment by being enclosed in soft capsules.
Do soft gel pills dissolve in water?
Soft gel pills are designed to dissolve in the digestive system rather than in water. They have a gelatin-based outer shell that can swell and eventually dissolve when it comes in contact with liquid, but they typically require the warmth and acidity of the stomach to dissolve fully and effectively. In plain water, the dissolution process will be much slower and less effective compared to the digestive environment.
What are the disadvantages of softgels?
The contents of softgel capsules may not be suitable for certain drugs in liquid, gel, or semi-solid form, which limits their application. Soft capsules are usually more expensive to manufacture than tablets or capsules, resulting in relatively high selling prices. As soft capsules are prone to rupture or leakage, they need to be more careful during storage and transportation. The rate at which softgel shells dissolve in the gastrointestinal tract may be affected by temperature and humidity, which can affect drug release and absorption.
What kind of gelatin is used in softgels?
The gelatin used in softgel capsules is mainly derived from animal collagen, which is usually derived from pig skin, cow skin and cow bone. Gelatin is a colorless, translucent solid material with good biocompatibility and degradability, making it an ideal material for medicinal capsules. The pharmaceutical industry often uses gelatin as the main ingredient in soft capsules to help encapsulate and carry liquid or semi-solid drugs. This gelatin not only has good molding properties, but also dissolves in the digestive system, thus helping the drug to be released into the body. When selecting gelatin sources, manufacturers often follow strict hygiene and safety standards to ensure the purity and safety of the product. In addition, plant-based alternatives such as AGAR or carrageenan have appeared on the market in order to cater to vegetarians or avoid certain religious and cultural restrictions.
What kind of gelatin is normally used in capsules?
The gelatin commonly used in capsules is bovine (cow) or porcine (pig) gelatin. These gelatins are derived from the collagen in the skin, bones, and connective tissues of the animals and are processed to create a substance that is both flexible and stable at room temperature.
In addition to bovine and porcine gelatins, vegetarian or vegan capsules are also available, often made from plant-derived substances such as hydroxypropyl methylcellulose (HPMC) or pullulan. These options are particularly important for individuals who avoid animal products for dietary or ethical reasons.
What are tablets more suitable for?
For chemically stable, accurate dosage requirements, moderate solubility of API, can be made into tablets. Tablets provide precise dose control and are suitable for medications requiring long-term stability or slow-release effects, with low production costs. For drugs acceptable to patients, tablets are easy to swallow and avoid the taste problems of liquid drugs. Tablets are also suitable for drugs that require large-scale production, are more economical, and are easy to store and transport. If the drug has no special dissolution problems or bioavailability requirements, tablets are an ideal choice.
What are hard capsules more suitable for?
Hard capsules are suitable for situations where a powder, granule or pellet drug needs to be encapsulated. Suitable for most solid drugs, especially those APIs that are not suitable for pressing directly into tablets, hard capsules can provide better dose control. Hard capsules are suitable for controlled, slow or delayed release of drugs, especially by changing the size of the shell material or drug particles to regulate the release rate. In addition, hard capsules have better stability and are easier to swallow, especially for oral drugs. They also prevent the medication from coming into contact with air, reducing the risk of oxidation or delixing. Hard capsules are usually produced with a mature process and low cost, which is suitable for mass production and commercialization.