Nikogul Significant expansion of the chapter on controlled release medication has been made to cover in a broader perspective, the principles employed in the design of such dosage forms, their classification and brief description of the technologies and products delivered by various routes. Fritz first used this method to distinguish the aromatic and aliphatic amines by using the perchloric acid as titrant. This biopharmaceutjcs ensures the drug release at the alkaline pH region where the drug has got maximum solubility. Lowitz first prepared the moisture-free solvents non-aqueous solvents.
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You are on page 1of Search inside document 1 Introduction Drugs, whether obtained from plant, animal or mineral sources or synthesized chemically, are rarely administered in their pure chemical form.
Earlier, it was believed that the therapeutic response to a drug is an attribute of its intrinsic pharmacological activity. But today, it is very much understood that the dose-response relationship obtained after drug administration by different routes—for example, oral and parenteral, are not the same. Variations are also observed when the same drug is administered as different dosage forms or similar dosage forms produced by different manufacturers, which in turn depend upon the physicochemical properties of the drug, the excipients present in the dosage form, the method of formulation and the manner of administration.
A new and separate discipline called biopharmaceutics has therefore been developed to account for all such factors that influence the therapeutic effectiveness of a drug. Biopharmaceutics is defined as the study of factors influencing the rate and amount of drug that reaches the systemic circulation and the use of this information to optimise the therapeutic efficacy of the drug products.
The process of movement of drug from its site of administration to the systemic circulation is called as absorption. The concentration of drug in plasma and hence the onset of action, and the intensity and duration of response depend upon the bioavailability of drug from its dosage form. Bioavailability is defined as the rate and extent amount of drug absorption. Other processes that play a role in the therapeutic activity of a drug are distribution and elimination. Together, they are known as drug disposition.
The movement of drug between one compartment and the other generally blood and the extravascular tissues is referred to as drug distribution.
Since the site of action is usually located in the extravascular tissues, the onset, intensity and sometimes duration of action depend upon the distribution behaviour of the drug. The magnitude intensity and the duration of action depend largely upon the effective concentration and the time period for which this concentration is maintained at the site of action which in turn depend upon the elimination processes.
Elimination is defined as the process that tends to remove the drug from the body and terminate its action. In order to administer drugs optimally, knowledge is needed not only of the mechanisms of drug absorption, distribution, metabolism and excretion ADME but also of the rate kinetics at which they occur i.
Pharmacokinetics is defined as the study of time course of drug ADME and their relationship with its therapeutic and toxic effects of the drug. The use of pharmacokinetic principles in optimising the drug dosage to suit individual patient needs and achieving maximum therapeutic utility is called as clinical pharmacokinetics. Figure 1. Schematic illustration of pharmacokinetic processes Drug administration and therapy can now be conveniently divided into four phases or processes: 1.
The Pharmaceutical Phase: It is concerned with — a Physicochemical properties of the drug, and b Design and manufacture of an effective drug product for administration by a suitable route. The Pharmacokinetic Phase: It is concerned with the ADME of drugs as elicited by the plasma drug concentration-time profile and its relationship with the dose, dosage form and frequency and route of administration. In short, it is the sum of all the processes inflicted by the body on the drug.
The Pharmacodynamic Phase: It is concerned with the biochemical and physiologic effects of the drug and its mechanism of action. It is characterized by the concentration of drug at the site of action and its relation to the magnitude of effects observed. Thus, in comparison — Pharmacokinetics is a study of what the body does to the drug, whereas Pharmacodynamics is a study of what the drug does to the body.
Pharmacokinetics relates changes in concentration of drug within the body with time after its administration, whereas Pharmacodynamics relates response to concentration of drug in the body. The Therapeutic Phase: It is concerned with the translation of pharmacological effect into clinical benefit. A schematic representation of the various processes involved in the therapy with a drug is given in Fig.
Knowledge of the factors affecting the bioavailability of drug helps in designing such an optimum formulation and saves many drugs that may be discarded as useless. On the other hand, rational use of the drug or the therapeutic objective can only be achieved through a better understanding of pharmacokinetics in addition to pharmacodynamics of the drug , which helps in designing a proper dosage regimen the manner in which the drug should be taken.
This obviates the use of the empirical approach where a considerable experimentation is needed to arrive at the balance between the desired therapeutic and the undesired toxic effects in order to define an appropriate dosage regimen. The knowledge and concepts of biopharmaceutics and pharmacokinetics thus have an integral role in the design and development of new drugs and their dosage forms and improvement of therapeutic efficacy of existing drugs.
However, majority of drugs are administered extravascularly, generally orally. If intended to act systemically, such drugs can exert their pharmacological actions only when they come into blood circulation from their site of application, and for this, absorption is an important prerequisite step.
Drug absorption is defined as the process of movement of unchanged drug from the site of administration to systemic circulation. Following absorption, the effectiveness of a drug can only be assessed by its concentration at the site of action. However, it is difficult to measure the drug concentration at such a site. Instead, the concentration can be measured more accurately in plasma. There always exist a correlation between the plasma concentration of a drug and the therapeutic response and thus, absorption can also be defined as the process of movement of unchanged drug from the site of administration to the site of measurement i.
This definition takes into account the loss of drug that occurs after oral administration due to presystemic metabolism or first-pass effect.
Plots showing significance of rate and extent of absorption in drug therapy. Not only the magnitude of drug that comes into the systemic circulation but also the rate at which it is absorbed is important. This is clear from Fig. A drug that is completely but slowly absorbed may fail to show therapeutic response as the plasma concentration for desired effect is never achieved. On the contrary, a rapidly absorbed drug attains the therapeutic level easily to elicit pharmacological effect.
Thus, both the rate and the extent of drug absorption are important. Such an absorption pattern has several advantages: 1. Lesser susceptibility of the drug for degradation or interaction due to rapid absorption. Higher blood levels and rapid onset of action.
More uniform, greater and reproducible therapeutic response. Drugs that have to enter the systemic circulation to exert their effect can be administered by three major routes: 1. The Enteral Route: includes peroral i.
The GI route is the most common for administration of majority of drugs. The Parenteral Route: includes all routes of administration through or under one or more layers of skin. While no absorption is required when the drug is administered i.
The Topical Route: includes skin, eyes or other specific membranes. The intranasal, inhalation, intravaginal and transdermal routes may be considered enteral or topical according to different definitions. Table 2. TABLE 2.
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