Drugs drug release profile

The process of formulation for any of the above is generically the same, beginning with some form of product specification and ending with one or more formulations that meet the requirements. Correct choice of additives or excipients is paramount in the provision of efficacy, stability, and safety. For instance, the excipients may be chemically or physically incompatible with the drug or they may exhibit batchwise variability to such an extent that at the extremes of their specification they may cause failure in achieving the desired drug release profile. In addition, some excipients, especially those that are hydroscopic, may be contraindicated if the formulation is to be manufactured in tropical countries. Flence formulators must work in a design space that is multidimensional in nature and virtually impossible to conceptualize. 

Iyer et al. [50] investigated the effects of roto-granulation on the performance of hydroxypropyl methylcellulose (HPMC), gelatin, and poly(-vinylpyrrolidone) (Povidone, PVP). In this process, all three binders produced similar results. However, HPMC was preferred due to prolonged drug release profiles, smaller particle size, and better content uniformity. 

In order to produce an adequate tablet formulation, certain requirements, such as sufficient mechanical strength and desired drug release profile, must be met. At times this may be a difficult task for the formulator to achieve, due to poor flow and compactibility characteristics of the powdered drug. This is of particular importance when one only has a small amount of active material to work with and cannot afford to make use of trial-and-error methods. The study of the physics of tablet compaction through the use of instrumented tableting machines (ITMs) enables the formulator to systematically evaluate his formula and make any necessary changes. 

Fig. 8.12 Comparison of drug-release profiles recorded in simulated gastric medium (pH =2) for (a) ibuprofen-AMP nanocomposite and (b) control sample (ibuprofen-talc suspension).

The erosion of copolymers requires the hydrolytic cleavage of three bond types the A A bond, the A-B bond, and the B-B bond. If the degradation rates of these three bonds are unequal, as is likely the case, then the erosion will be inhomogeneous. And, if drugs are inhomogene-ously distributed in the polymer matrix, the drug release profile will not follow overall device erosion (Shen et al., 2002). Therefore, it is necessary to accurately describe the microstructure of microphase-separated systems. 

In their study of branched PSA, Maniar et al. (1990) found that the molecular architecture of branched polymers affects the release kinetics in a variety of ways. They found that the branched polymers degraded faster than linear PSA of comparable molecular weight (Maniar et al., 1990). They also noted that drug (morphine) release profiles were more characteristic of bulk erosion than surface erosion An initial lag time during which very little drug was released was associated with the time required for water to swell the polymer. This was followed by a period of relatively fast release, which tapered off as the device disintegrated. The polymer matrix lost its mechanical integrity before the release experiment was complete (Maniar et al., 1990). Despite the increase... 

The simplest model for pure erosion control with kinetics dominated by a single rate constant and uniformly distributed drugs was described by Hopfenberg (1976). This model says nothing about the various physical phenomena that contribute to erosion, and therefore fails to describe drug release profiles from many poly anhydride systems. Below we classify some of the models that can be found in the literature. 

FIGURE 6.41 Comparison of drug release profiles obtained by HPLC and by /iPLC, as reported by Liu... 

This chapter provides an introduction to the pharmaceutical sector, and the business of developing new active pharmaceutical ingredients (API). Crystallization is the preferred method of isolating commercial API products because it offers a highly efficient means of purification. The crystallization process is also where the physical properties of the drug substance are defined. These properties can have a significant impact on the formulated product and process, and eventually on the drug release profile in the patient. 

One challenge that remains in biopharmaceutics research is that of correlating in vitro drug-release profiles with the in vivo pharmacokinetic data. TVIVC has been defined by the... 

Joergensen K, Jacobsen L. Factorial design used for ruggedness testing of flow through cell dissolution method by means of Weibull transformed drug release profiles. Inti J Pharm 1992 88 23-29. 

Figure 2 Simulated in vitro drug-release profiles (panels a and b) and resultant plasma concentration—time profiles for a drug with a 1—hr half-life (panel c) and a 6—hr half-life (panel d).

Table 1 Comparison of Predicted Pharmacokinetic Parameters for Two Different Drugs with Identical In Vitro Drug Release Profiles, But Different Drug Disposition Characteristics (ty2 = 1 or 6 hr)...

Table 2 Fitted Weibull Parameters for the Three In Vitro Drug-Release Profiles Shown in Figure 3...

For an extended-release dosage form, at least three test time points are chosen to characterize the in vitro drug-release profile for the routine batch-to-batch quality control for approved products. Additional sampling times may be required for formulation development studies, biopharmaceutical evaluations, and drug approval purposes. An early time... 

Prior to formulating a drug substance into a dosage form, the desired product type must be detemined for planning the product formulation activities. Then, various initial formulations are developed and then evaluated for selected parameters, such as drug-release profile, bioavailability, clinical effectiveness, and for any scale-up problems. The best formulation is selected and becomes the master formula. Each batch of the product subsequently prepared must meet the specifications established in this master formula. 

Drug release profiles from the tablets in various dissolution media are shown in Fig. 2. In all cases the release rates decreased initially from the control (distilled water) as electrolyte concentration increased, until a minimum release rate was obtained. As the electrolyte concentration further increased the release rates similarly increased until a burst release occurred. These initial decreases in release rates were probably coincident with a decrease in polymer solubility, in that as the ionic strength of the dissolution medium is increased the cloud point is lowered towards 37°C. It may be seen from Table 5 that minimum release rates occurred when the cloud point was 37°C. At this point the pore tortuosity within the matrix structure should also be at a maximum. It is unlikely to be an increase in viscosity that retards release rates since Ford et al. [1] showed that viscosity has little effect on release rates. Any reduction in hydration, such as that by increasing the concentration of solute in the dissolution media or increasing the temperature of the dissolution media, will start to prevent gelation and therefore the tablet will cease to act as a sustained release matrix. 

Table 2—In vitro drug release profile of microcapsules and micromatrices...

The drug release profile was plotted against time (Figs. 4 and 5) and it was observed that the release kinetics followed both first-order and Higuchi equations up to 75-80% of the cumulative drug release. The micromatrices followed the Higuchi equation (NONLIN package). 

No single polymer can match all of the above criteria. This has led companies to develop application-specific polymers and/or series of polymers that may have the structure property variability to encompass all potential applications. As listed in Table 3, several properties of the polymer have a direct effect on its degradation kinetics and consequently on the drug release profile. Hence novel polymers that... 

The property that makes polyanhydrides unique is their surface hydrophobic-ity. Due to this high hydrophobicity, polyanhydride matrices do not facilitate water absorption. Consequently, hydrolytic degradation is restricted to the surface—a property that is termed as surface erosion. This type of degradation allows for zero-order release of drugs, i.e., the drug release profile is independent of the residual concentration of the drug in the matrix. 

In an effort to develop an effective bioadhesive system for buccal administration, insulin was encapsulated into polyacrylamide nanoparticles by the emulsion solvent evaporation method [98]. Though nanoparticle formation ensures even distribution of the drug, pelleting of the nanoparticles was performed to obtain three-dimensional structural conformity. In addition, it was hypothetized that the pelletized particles will remain adhered to the mucosa, leading to good absorption. While studying bioadhesion and drug release profiles, it was found that the... 

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