Showing posts with label Absorption of drugs. Show all posts
Showing posts with label Absorption of drugs. Show all posts

Factors affecting solubility and dissolution rate of crystalline and amorphous forms.. ampicillin, caffeine, theophylline, glutamide, mercaptopurine

Solubility and Dissolution Rates of Crystalline and Amorphous Forms

The solubility and dissolution rates of crystalline and amorphous forms of drugs can vary significantly, affecting their bioavailability and therapeutic efficacy. Here's a breakdown of the factors involved and some specific examples you mentioned:

Factors Affecting Solubility and Dissolution Rate:

- Crystallinity:

Crystalline forms have a more ordered structure, leading to stronger intermolecular forces and generally lower solubility compared to their amorphous counterparts.

- Surface area:

Amorphous forms have a larger surface area due to their irregular structure, increasing their contact with the solvent and potentially leading to faster dissolution.

- Hydrogen bonding:

Some drugs form strong hydrogen bonds with water molecules, which can hinder their dissolution in crystalline forms. Amorphous forms may have different hydrogen bonding patterns, influencing their solubility.

- Porosity:

Crystalline forms can have internal channels or pores that can trap solvent molecules, slowing down dissolution. Amorphous forms typically lack such porosity, potentially enhancing dissolution.

Specific Examples:

- Ampicillin:

Both crystalline and amorphous forms of ampicillin are readily soluble in water. However, the amorphous form exhibits a slightly faster dissolution rate due to its higher surface area.

- Caffeine:

Crystalline caffeine is less soluble than its amorphous form. The amorphous form dissolves about 3-5 times faster due to its higher surface area and lack of strong intermolecular forces in the crystal lattice.

- Theophylline:

Similar to caffeine, crystalline theophylline is less soluble and dissolves slower than its amorphous form. The amorphous form has a significantly higher dissolution rate due to its increased surface area and reduced hydrogen bonding with water molecules.

- Glutamide:

Both crystalline and amorphous glutamide are highly soluble in water. However, the amorphous form exhibits a slightly faster dissolution rate due to its higher surface area and potentially different hydrogen bonding patterns.

- Mercaptopurine:

Crystalline mercaptopurine is poorly soluble in water, while its amorphous form is significantly more soluble and dissolves faster. The amorphous form has a higher surface area and lacks the strong intermolecular forces present in the crystalline structure.

Overall:

The relationship between crystallinity and dissolution rate is complex and depends on various factors. While amorphous forms generally dissolve faster due to their higher surface area and potentially altered intermolecular interactions, other factors like hydrogen bonding and porosity can influence the rate in specific cases.

It's important to note that the therapeutic efficacy of a drug can be affected by both its solubility and dissolution rate. Faster dissolution can lead to quicker absorption and onset of action, while lower solubility might require higher doses or different administration routes to achieve the desired effect.

The strength of the drug effect .. The speed of absorption of the drug using an injection syringe vein and provides the controlled and slow release of the drug

The speed of initiation of the drug's effect is determined by the speed of the drug absorption and in the peripheral cases where an intravenous injection pill is used which has immediate effect and usually has a drug effect. It provides the controlled and slow release of the drug and the slow release that is not necessarily oral, where the onset of the effect is long and slow In order to achieve desired therapeutic qualities.
The strength of the drug effect is usually traced to the drug concentration that reaches the circulation. The real relationship between pharmacokinetics and pharmacokinetic dynamics is often complex, but it can be generalized that high-dose cyclic concentrations lead to a stronger effect.

Correlation of dosage levels, absorption efficiency, total bioavailability, distribution, filtration and susceptibility to lipid breakdown

Tracking the levels of the circulating drug achieved for the dose, absorption efficiency, total bioavailability, distribution and clearance. The largest determinant of the size of the drug distribution is its ability to dissolve fat. The higher the lipid solubility, the greater the drug's ability to cross the biofilms and move to the extravascular environment, especially to the liposuction and central nervous system (CNS).
Many drugs are associated with plasma proteins, especially plasma albumin. However, although plasma drug binding is dynamic and inverse, any drug associated with a specific time is bound to the size of the plasma and thus can not participate in extracellular distribution.

The relationship of filtration with dosage levels in rotation.. Drug absorption and the relationship between pharmacokinetics and pharmacodynamics

Clearance is the last factor influencing drug levels in turn. The levels of the drug are reduced by rotation as they are eliminated faster as a result of metabolism or other processes (ie, half-life decreases). Higher circulatory levels are difficult to achieve when the drug filter is high with low pharmacological filtration, and it is unlikely that drug buildup will occur with high circulating filtering and dose repetition.
It is important to understand all these factors before the properties of the drug, especially the relationship between pharmaceutical pharmacokinetics and pharmacodynamic pharmacodynamics, which can fully distinguish the expected effect of the drug.
Both pharmacological and pharmacological factors are affected by drug distribution and filtration only. In general, they can only be altered by some types of interactions. Drug absorption and bioavailability are significantly affected by drug administration, dosage form, and drug sharing with other substances.
Some large payments of pharmaceutical research have been devoted to the last two decades.

The objectives of drug absorption.. The process that determines the compounds that penetrate one or more of the cellular membranes in order to be able to enter the body

Suction can be defined as a process that identifies compounds that penetrate one or more cellular membranes in order to be able to enter the body.
Absorption should not be confused with bioavailability, which describes the entry of the described compounds into systemic rotation.
Absorption and bioavailability may be similar for some medications and dosage speeds, such as the dose of intravenous dose. In many cases, however, this is not the case.
For a drug that is not subject to any metabolic shift between the next direct site of absorption and the entry into systemic rotation, the absorption and bioavailability are likely to be identical. All absorbed drugs reflect systemic circulation, regardless of whether the drug can be altered or altered by other methods: before absorption.
On the other hand, any drug that takes place somewhere between post-absorption and systemic circulation, systemic availability-bioavailability-will be less than absorption.
The drug given orally passes the first large hepatic pathway and can lead to a decrease in oral bioavailability even though it is effectively absorbed from the gastrointestinal tract to the visceral circulation.
The pharmacological efficacy of the systemic effect of the drug is a function of its internal activity and the concentration of the concentration in circulation.
The speed of onset of effect, intensity, and duration of effectiveness are indications of concentration.

Medicinal methods of medicine .. Avoid high absorption of the drug in the visceral circulation and the possibility of metabolism in the first hepatic passage

The methods of delivery of the injectable medicine are those methods that do not lead to a high absorption of the drug in the splanchnic circulation, and thus avoid the possibility of metabolism of the first hepatic passage. It should be noted that some injections do not avoid the effects of other first-generation metabolism (eg pleural metabolism of some inhalatory drugs).
Some of the main methods of administering the drug include the arterial pathway, intrathecal, intravenous, transdermal, nasal, buccal, intraperitoneal, vaginal and rectal.

Injection of drugs into the artery .. delivery of drugs to the organs directly in the chemical treatment of cancer and the use of Vasobricin to bleed the digestive system and treatment of malignant neoplasm

Intravenous injections are usually used to deliver drugs directly to organs, for example in chemotherapy for cancer, and in the use of vasopressin in cases of gastrointestinal bleeding. Carotinin intracellular injection is effective for the treatment of cancerous tumors. Injection of actinomycin D is also used for pelvic intra-arterial treatment of trophoblastic disease.
The administration of the drug through the artery has the potential for safe results, reports have been reported on the possibility of embolization, arterial occlusion, and topical drug toxicity.

Injection of the drug into the spinal cord fluid.. Full bioavailability within the central nervous system of drugs that cross the cerebral hemorrhage to treat meningitis and ventricular

Injections within the spinal cord fluid directly guarantee full bioavailability within the central nervous system of drugs that can cross the blood-brain barrier. These dosage methods are used to treat serious neurological infections in the central nervous system such as meningitis and ventricular inflammation and are used with spinal anesthesia agents such as mebivacaine and bilocarpine. The drugs injected into the flock are initially spread in about 140 ml of cerebrospinal fluid, so this method gives high concentrations within the central nervous system with less systemic toxicity risk.

Intravenous injection of medicine.. Direct drug entry into the venous circulation of general anesthesia and to treat arrhythmias and preclinical tests of compounds

Giving the medicine intravenously leads to the drug entering directly into the venous circulation. The shape of the rotational drug is determined by the size, speed and duration of injection. A venous thrombosis is used for the direct therapeutic effects, typical of general anesthesia and for treatment of cardiac arrhythmia, and intravenous doses are commonly used during the development of the drug for preclinical testing of compounds and also as a measure of absolute bioavailability for other dosage methods.

Intramuscular injection of drugs .. Drugs and vaccines that do not absorb orally, such as aminoglycoside, insulin and hepatitis vaccines

After the intramuscular injection, drugs must pass one or more vital membranes to reach the systemic circulation.
Intramuscular injections are used primarily for non-absorbent drugs and vaccines such as aminoglycosides, insulin and hepatitis vaccines. The speed of the intramuscular pathway is usually used for adjuvant therapies and specialized signals developed to provide slow delivery of drugs in this way, such as water slides, oil ointments, complexions and conservatives of the microencapsulation class.

Drug injection by dermis.. Suboptimal treatment of scopolamine. Clonidine, estradiol, nicotine, nitroglycerin and scopolamine

Since the introduction of subcutaneous treatment of scopolamine, many dendritic delivery systems have been developed for systemic effectiveness. The most important advantages of the delivery route include the continuous release of the drug within a specified time and a few pre-systemic clearance, the possibility of easily withdrawing the medicine by simple removal of the drug delivery device, and is convenient for the patient.
Some of the disadvantages of this route are due to the skin-related properties of the skin and skin interactions and the relatively large size of the dose.
Dermal delivery is an effective option only in drugs that are generally given in small doses (<10 and="" approved="" clonidine="" commonly="" drugs="" estradiol="" good="" have="" include="" membrane="" mg="" nicotine="" nitroglycerin="" p="" penetration="" properties.="" scopolamine.="" which="">

The nasal way of injecting the drug .. Dissolution of the drug in the nasal and fatty mucus to cross the nasal epithelium. Insulin injections and sex hormones

The application of the drug to the nasal route may be used for systemic or situational effects. Topical effects include nasal allergies, rhinitis and nasal congestion. Methods of nasal application of systemic effects have proven effective for a small number of drugs and are being tested for the use of many other drugs.
The sophisticated structure and specialized function of ventilation and membranes in the nasal cavity as well as the small surface area of ​​this area may limit the ability to deliver the drug.
The effect of chronic drug exposure on the safety of nasal membranes should be taken into account. This problem may increase the need for surface agents to achieve a good penetration of this pathway.
In spite of these factors, the physical properties of these compounds for optimal nasal absorption are the same as for other absorption methods. The drug must dissolve in the nasal mucosa and must be sufficiently soluble in fat to cross the nasal nasal membrane. Nasal absorption is facilitated by the high permeability of the vein and venous-related veins. Various delivery devices were adopted by way of nasal drugs to apply droplets, capsules, nebulizers and matrices.
The small peptide particles are suitable for nasal delivery and vasopressin and oxytocin are commercially available for nasal doses. Antibodies and antagonists of the thyroid-stimulating hormone and other vasopressin antagonists and peptides are tested. The nasal route has produced remarkable results in animals for sex hormones. Insulin delivery was tested on this route but was moderately successful.

The narrow way of injecting the drug.. The absorption under the tongue and the neck Use of nitroglycerin to treat attacks of headache and ambulance in angina

The primitive knowledge of sublingual and anal absorption was demonstrated by the use of nitroglycerin in these methods to treat headache and ambulance attacks in angina.
The drug can be absorbed alone through the oral cavity or under the tongue. It appears clearly that sublingual absorption is faster than other methods due to sublingual membranes and heavy blood feeding.
The average saliva saliva is approximately 6, so the absorption of drugs is likely to be naturally active, as it is to help the fixed molecules and acids with a pKa value greater than 3 and the bases with a pKa value of less than 9.
The compounds marketed to give by the narrow or subcutaneous route include organic nitrates, barbiturates, papaverins, trypsin, brocculphirazine, benzodiazepines, buprenorphine, trypsin, captopril, isoprenalin, oxytocin and nifedipine. Currently, oxytocin is the only peptide marketed for sublingual administration.
The application of sublingual steroids has been tested and has been moderately successful.

Inhalation of the medication .. exposure to nasal or oral membranes, pharynx, trachea, bronchial tubes, capillaries, air bags and climate

When the substance is inhaled, it is exposed to nasal or oral membranes, pharynx, trachea, bronchial tubes, air sacs, and air sacs.
The lung has a surface absorption area of ​​about 70 square meters, which is larger than the surface of the micro-absorbent. However, lung and associated airways have been adopted to prevent access to compounds described to high-absorbent peripheral lung surfaces. The device is designed to prevent access to the molecular material. However, if the substances reach the peripheral region of the lung, the absorption will be very effective. Both the particle size and the speed of application control the permeability of the inhaled material to the airway space. The optimum size of the particles so that they can penetrate the airway in depth is about 3-5 micrometers and will emulate the large particles of the upper airway.
Most inhalation devices can deliver approximately 10% of the applied dose to the lower respiratory tract. Many methods have been developed to increase pulmonary delivery. The drug was given to 21% when the pressurized metered dose inhaler was used. Despite these advantages, the administration of pneumonia remains ineffective.
The systemic availability of inhaled drugs can be inhibited by first pulmonary embolism.
The lung contains many drug metabolism enzymes that contain mixtures of the functions of oxidase, monosamine and esterase. Several models of animals, especially rat, rabbit and dog, are used in the study of drug inhalation.

Intraperitoneal injection.. Chemical treatment of peritoneal tumors. Peritonitis in patients with renal impairment treated with continuous mobile pharyngitis

It is not common to apply peritoneal medications. This delivery route is often used to manage and develop preclinical compounds, and its clinical use has been limited to chemotherapy for peritoneal tumors.
Peritotonotis is frequently present in patients with renal impairment who receive continuous mobile bypass treatment (CAPD). Peritonitis is often associated with systemic infection, so therapeutic levels of antibiotics must be achieved in both the peritoneal cavity and within the systemic circulation.
Drugs may be given orally or in order to achieve sufficient systemic levels in the hope of achieving therapeutic levels in the peritoneal cavity. Alternatively, drugs may be applied directly into the peritoneal cavity to reach systemic levels through peritoneal absorption. According to the author's knowledge, there is little clear information about the relative efficiency of these alternatives.

Vaccine injection in the vagina.. Blood feeding of the vagina through the uterine and pharyngeal arteries. Steroidal and vaginal contraception and microbial microorganisms

The length of the fibroblastic channel in the human vagina is 10-15 cm extending to the top and behind the vagina vulva and lower cervical uterine cervix. The blood feeding of the vagina is through the uterine and perineal arteries and is leaking out of the vagina through a rich plexus that flows into the intracranial vein. The surface of the vaginal epithelium maintains its moisture through cervical secretions. The vaginal fluid is diluted between 4-5.
Vaginal delivery is used for localized effects, but vaginal absorption can increase to the speed and effectiveness of systemic delivery. Good systemic absorption, as well as the ability of the vagina to stabilize the delivery devices, affect many forms of vaginal forms, especially steroid contraceptives. A large number of Vaginal Regulated Vaginal Regression forms are available including vaginal rings and microbial microbial spheres to recognize biodegradable microspheres.

Injecting the medicine in the rectum .. The compounds that are absorbed in the lower rectum avoid the metabolism of the first hepatic pathway and slower than the oral absorption

The length of the human rectum ranges from 15-20 cm. It is naturally empty and contains 2-3 ml of 7 to 8 mL mucosal fluid and does not contain villi and has a limited surface absorption area of ​​about 200-400 cm 2. The subcutaneous mucosa is rich in blood vessels and lymphocytes. The discharge of the vein from the upper rectum to the portal circulation while the vein is discharged from the rectum, middle and lower directly in the inferior vena cava and there are many anastomoses that extend between these veins, making it difficult to distinguish the exact anatomy. The compounds that are absorbed in the lower rectum appear to avoid the metabolism of the first hepatic pathway, unlike the compounds absorbed in the upper rectum. The rectal absorption is usually slower than oral absorption, but rectal absorption is assumed to exceed oral absorption due to avoidance of the first hepatic passage after rectal delivery for certain drugs such as morphine, mitochloropamide, argotamine, lidocaine and propranolol. Where systemic bioavailability in humans for the lidocaine is 65%, compared to 30% after oral administration.
Usually, rectal absorption of drugs with aqueous or alcoholic solutions is greater than suppositories. Non-active substances on the surface such as salicylates, rectal absorption of water-soluble drugs, and high molecular weight compounds such as insulin, heparin, and gastrin are also lacking.

The blood flow of the digestive system related to the absorption of drugs .. A network of capillaries from the visceral circulation The drugs are picked up by lymph vessels

GI blood flow in Relation to Drug Absorption
Drugs may move away from the serosal side of the digestive tract by one or two mechanisms.
The digestive system provides a network of capillaries from the splanchnic circulation. It is possible that the drugs are picked up by the lymphatic vessels in the epithelium of the digestive system and transmitted through the lymphatic system, which distracts the abdominal region of the abdominal area into the thoracic duct. Any drug is absorbed by this device, which enters the systemic circulation directly and is not exposed to the first liver passage. Most of the drugs are predominantly absorbed by the capillary system with visceral circulation, although both the capillaries and the lymphatic system exist.
The reason for this seems to be the relative velocity of blood and lymph flow. The blood flow velocity in the visceral circulation is 1 - 1.5 l / min or 30% of the product of the heart. This can increase to 2 liters / minute after a meal. While the flow velocity of the lymph during the same area is only 1-2 ml / min, but can increase to 5-20 ml / min after a meal. Thus, the lymph flows in this area less than the blood flow by about 500-700 times. The relative velocity of the visceral blood flow provides the actual penetration conditions on the parietal side of the digestive tract epithelium and also ensures a high concentration gradient. These conditions increase the effective absorption into the blood stream more than the lymph.
Only a few drugs are absorbed by the lymph system. These drugs include drugs with high molecular weight that can not enter capillaries and dedicated molecules such as steroids.

Hepatic First-Pass Metabolism.. Absorption of drugs in the stomach and intestines to the visceral circulation and the vein of the door and liver

Hepatic First-Pass Metabolism:
Most of the drugs that are absorbed in the stomach and intestines pass through the visceral circulation, which leads to the portal vein and the liver and then to the general circulation. Vehicles absorbed by this route must cross the liver and will initially operate at higher concentrations than in the case that eventually distributes to the general circulation and any other place.
Because hepatic metabolism is the first naturally occurring, a high proportion of any oral medication will metabolize significantly in the first trimester. The drug can be effectively absorbed from the digestive tract and its bioavailability is low in general circulation as a result of the first hepatic cirrhosis. For example, high-extraction drugs, which include asepotolol, albrenolol, desipramine, isopropyrineol and lidocaine.
Subscribe to: Posts (Atom)