Chemical stability, of a drug

There are several parameters that affect the solubility and chemical stability of a drug in solution. The pH of the solution can dramatically affect both the solubility and chemical stability of the drug. Buffer concentration/composition and ionic strength can also have an effect, especially on chemical stability. The hydropho-bic/hydrophilic nature of the drug influences solubility. A typical characterization of a dmg will start with a study of the chemical stability of the drug as a function of pH. The structure of the degradation products will be characterized to determine the mechanism of the degradation reaction. 

Micellar solutions may also be used to increase the chemical stability of a drug. Hence, since the micellar core is generally essentially free of water, there is typically a reduction of the hydrolysis rate on solubilization. As an example of this, Lin et al. found that the hydrolysis of indomethacin was lowered when it was solubilized into PEO-PPO-PEO block copolymer micelles (148). In particular, the hydrolysis rate was reduced at higher copolymer concentrations and molecular weights (constant EO/PO ratio), which follows the solubilization capacity of these block copolymers (Figure 1.10). 

The optimized drug product may be viewed as a drug-delivery system for the one or more drugs that it contains. The goal of this drug-delivery system is to release the drug(s) to produce the maximum simultaneous safety, effectiveness, and reliability, as depicted in Fig. 9. Various physicochemical product properties that influence the quality features of safety, effectiveness, and reliability are shown in Table 6. Some physicochemical properties can affect two or all three quality features of Fig. 9. For example, consider chemical stability. As a drug decomposes, if the... 

The physical properties of an API can significantly effect the physical and chemical stability of a formulation, its bioavailability and ultimately they can modify the pharmacokinetic profile of the drug. This issue will be discussed in more detail in section 3.4. For these reasons it is necessary to control the physical form of the API at the Pures crystallization step, and throughout the subsequent formulation steps, to ensure a consistent delivery profile to the patient. This control strategy must be documented in the New Drug Application... 

In considering chemical stability of a pharmaceutical, one musf evaluate the reaction order and reaction rate. The reaction order may be the overall order (the sum of the exponents of the concentration terms of fhe rate expression), or fhe order with respect to each reactant (the exponent of the individual concentration term in the rate expression). The reaction rate expression is a description of the drug concentration with respect to time. Most commonly, zero- and first-order reactions are encountered in pharmacy. 

Badway, S. I. F., Gawronski, A. J., and Alvarez, F. J. (2001), Application of sorption-desorption moisture transfer modeling to the study of chemical stability of a moisture sensitive drug product in different packaging configurations, Int. J. Pharm., 223(1-2), 1-13. 

Often, stability of a drug has been referred to as the time from the date of manufacture and packaging until its chemical or biological activity is not less than a predetermined level of labeled potency without the physical characteristics changing appreciably. For most drugs, 90% of labeled potency is generally recognized as the minimum acceptable potency. 

Drugs in solution formulations may be more susceptible to chemical reactions leading to degradation. The most common reactions are hydrolysis, oxidation, and reduction. Usually, the reaction rate or type is inLuenced by pH. For example, the hydrolysis of acetylsalicylic acid (aspirin) is pH dependent, and its pH-rate proLle shows a large and complex variation dfrls to four distinct mechanistic patterns (Alibrandi et al., 2001). Therefore, it is essential to monitor and understand the chemical stability of the drug in pH-adjusted formulations. 

For instance, when the chemical stability of a suspension of ibuprofen powder and other ibuprofen-wax microspheres was studied with a modified HPLC procedure for three months, the amount of drug released from the microspheres was affected by the medium pH, type of suspending agent, and storage temperature without observing chemical degradation of the drug [49]. 

Cyclodextrins (CDs) have a wide range of application in the pharmaceutical field due to their unique structure, which allows them to include hydrophobic molecules in their apolar cavity and to mask the physicochemical properties of the included molecule. This results in the enhancement of drug bioavailability by improving aqueous solubility and the physical and chemical stability of the drug, masking undesired side effects such as irritation, taste, or odor, and overcoming compatibility problems or interactions between drugs and excipients. 

The stability of a drug in the gut is influenced by both chemical and enzymatic factors. Protection from chemical degradation may be accomplished via coating... 

A stabilizer is simply a formulation component without physiological effect that is added to the formulation to maintain the physical or chemical stability of the drug substance. As discussed in the previous section, the function of a surfactant may be to stabilize, and as control of pH is often critical to stability, one might consider buffers to be stabilizers. However, in this section we will address stabilizers other than surfactants or buffers. Further, as most of the stabilization literature deals with proteins, our discussion will focus on proteins, although in principle many stabilization principles apply to small molecules as well. 

The chemical and physical stability of a drug can influence the choice of dosage form, the manufacturing... 

An antibiotic dry syrup formulation is shown in Table 143 as an application of micronized crospovidone of low bulk density. The formulation has been developed in the laboratory for two different drugs, so that it can be regarded as a typical guide formulation. It contains citric acid, to adjust the pH to 4.9, to optimize the chemical stability of the drug, ampicillin trihydrate or amoxicillin trihydrate. 

Chemical Stability Chemical degradation of the drug includes reactions such as hydrolysis, dehydration, oxidation, photochemical degradation, or reaction with excipients. The constant presence of water and oxygen in our environment means that exposure to moisture or oxygen can affect the chemical stability of a compound. Chemical stability is very important, not only because a sufficient amount of the dmg is needed at the time of administration for therapeutic purposes, but also because chemical degradation products may adversely affect the properties of the formulated product and may even be toxic. 

For a successful formulation and delivery of peptides and proteins, it is crucial that the formulation scientist has a thorough knowledge of several factors the physical and chemical stability of the drug compound, the content of well-defined and selective excipients in the formulation, an optimized storage stability, and naturally, the route of... 

A large proportion of drug substances, whether neutral molecules, free adds, free bases or salts, are capable of exhibiting polymorphism or pseudopolymorphism (hydrate or solvate formation). It has been reported that 70% of barbiturates, 60% of sulfonamides and 23% of steroids exhibit polymorphism." Polymorphism often influences a range of physicochemical properties such as solubility, dissolution rate, stability and powder properties as well as bioavailability. Usually, it is possible to determine the most stable polymorph and discover recrystallization solvents that uniquely produce this form and improve the physicochemical and physicome-chanical properties and chemical stability of the drug. 

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