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IN-VITRO KINETICS OF DRUG RELEASE AND ITS MODELING
OBJECTIVE OF THE RESEARCH:-
- Development of in-vitrorelease kinetics of the Diclofenac Sodium.
- Describing Pharmacokinetics Models by using mathematical techniques.
- Estimation of released drug and its modeling.
- Enactment of the kinetic models.
- The main purpose of this study is to investigate thein-vitrorelease kinetics of the Diclofenac Sodium and its modeling .
A drug is an intrinsic material orit is a material obtained by some chemical process and it affects the functioning of the body when it is taken into a living body. A drug is used in thetreatment of disease orpreventionof a disease and is also used forreliefof anxiety. Here we discuss two ways to enhance a new drug. In in-vitro method new drug is developed by adopting the procedure that involves only test apparatus and does not involve laboratory, animals or humans and on the other hand, in in-vivo method new drug is developed by adopting the procedure that involves animals or humans .
Pain killers are medicines that reduce headaches, sore muscles andpains. There are many different painkillers. Some types of pain killers give better response to certain medicines than others. It is to be noted that the response to a pain killer may vary person to person , , .
Non-linear regression involves model fitting and assessment of coefficients of a given model. Regression theory entirely believes on the assessment procedure, called the method of least squares while in non-compartmental analysis assessment procedure is called the method of moments. In this method, plasma drug concentration is taken as a random variable. Often the investigation requires comparing this estimation for different drugs. Mathematical aspect of non-compartmental model involves a linear function , ,
Diclofenac sodium is a well known non-steroidal anti-inflammatory drug (NSAIDs) . It prevents from any one of the following three enzymes: cycloxygenase (COX), lipoxygenase and prostaglandin synthetase; or all these allow for the therapeutic actions. It gives relief in pain, inflammation, headache, fever and cancer etc , , . Generally, the side effects of this drug are; gastrointestinal disorders like diarrhea, indigestion, flatulence, stomach upset, decreased hunger. The half-life of Diclofenac sodium is about 1 to 3 hours; multiple dosing is required to keep the desired therapeutic level of drug. Controlled or sustained release dosage form is used to resolve these problems.. The chemical name is
2-[(2, 6-dichlorophenyl) amino] benzene acetic acid, monosodium salt. Its molecular weight is 318.14 and molecular formula is C14H10Cl2NNaO2. Also its structural formula is given as under. ,,.
Pharmacokinetics is the study of drug absorption, distribution, metabolism and excretion (ADME) and ‘what the body does to the drug’. The simplest pharmacokinetic model deals with the body as a single compartment in which a medicated drug distributes and from which the drug is eliminated also. Usually the rate of eliminated drug is proportional to the concentration of the drug used. When absorption and distribution have occurred, a single Compartment model approximates the clinical situation surprisingly well by first-order elimination. We make a start by considering this, and then characterize some important deviations from it , .
Drug release has been a significant topic in the field of drug delivery for many years. With improvement in material design and engineering, new materials with increasing complexity and having more functions have been introduced into the advancement of drug delivery devices and systems. Both naturally derived and synthetic macro molecules are extensively used in controlled drug release to maximize the effectiveness of the system and to facilitate the clinical applicability and it also improves the quality of life ,,. The procedure by which a drug leaves the product is called drug release ,,. There are many ways to describe the drug release.
- Immediate release
- Delayed release
- Extended release
- Controlled release
- Pulsatile release
STATEMENT OF TOPIC AND AIMS:-
Topic of the thesis is “IN-VITRO KINETICS OF DRUG RELEASE AND ITS MODELING”. The aim of this study is to assess thein-vitrokinetics of drug release and its modeling. The model drug that will be used for the research is Diclofenac sodium. Several mathematical models areused toevaluate the kinetics and means of drug release from the dosage form. Amodelisusedto express quantitative relationships. We select a model on the basis of correlationcoefficient() value that best fits the release data. The model involving higher value of “” is regarded as thebest model and is most suitable for the release data ,,.
The suitable models for fitting are:
- Zero order model
- First order model
- Higuchi model
- Hixson-Crowell model
- Korsmeyer-Peppas model
2:- LITERATURE REVIEW:-
The blood and other fluids of distribution administered the drug into the body. When the drug reaches at the place of action, they act by binding to sense organs called receptors. The receptors are located on the outer membrane of cells. Medical science has acquired knowledge about the action of drug on the body. The pharmacologists have recognized that the human body is full of different kinds of sense organs which give different response to different types of drugs. A few sense organs are very specific and other sense organs have less such specificity and give different responses to different types of drug molecules , , .
In pharmacokinetics, we determine the movement of drugs into and out of the body. Experimentally, the drug is distributed to a group of patients and then blood and urine specimens are taken for subsequent quantitative analysis , ,. Following processes are adopted by every drug entering into the body:
Pharmacokinetic analysis depends on estimation of total drug exposure. The total drug exposure is often estimated by the area under the curve and is calculated by using method of trapezoidal rule. Due to dependence on length of interval in trapezoidal rule, the area estimated is highly dependent in the blood/plasma sampling schedule. Statistical moments are computed by using trapezoidal rules. There are two main trapezoidal rules for calculation of area under the curve, namely linear and log linear rules ,. There are many numerical integration techniques for assessment of “area under the curve” and “area under the first moment time curve”. Hybrid methods are used in many computer software programs. The time from zero to infinity is required for an accurate evaluation of different kinetic parameters ‘’area under the curve’’ and ‘’area under the first moment time curve’’. The extrapolation from time of last measured concentration is done by integrating the curve fromto infinity , .
RELEASE KINETIC MODELING:-
Many kinetic models are set forth for specific release of drug. If some qualitative and quantitative changes are made in the formulation of drug, then drug release and in-vivo performance may be changed. It is always desirable that developing tools must make easy to develop the product by reducing the necessity of bio studies . Following methods are used for kinetic modeling on drug release.
- Statistical methods
- Model dependent methods
- Model independent methods
When analyzing pharmacokinetics data, we use non-compartmental analysis or non-linear regression analysis. The method is actually depending upon on what is required from the analysis. The method is used to determine the administration of drug. The trapezoidal rule is used for the measurement of the area under plasma concentration-time curve. This method is, generally, applied for the first order model. Huguchi plotted the obtained data between percentages of cumulative drug release and square root of time. The several types of modified release pharmaceutical dosage forms use this relationship to describe the drug dissolution .
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