Tablet formulations disintegrants

Stability, including the stability of the drug substance, the overall tablet formulation, disintegration, and the rate and extent of drug dissolution from the tablet for an extended period. 

Formulation. Compressed tablet formulations contain several types of inert, adjuvant ingredients necessary for proper preparation and therapeutic performance. Tablets designed to be swallowed need diluent, disintegrating, binding (adhesive), and lubricating inert ingredients, whereas... 

The Cadila system [13] has been designed to formulate tablets for drugs based on their physical (solubility, hydroscopicity, etc), chemical (functional groups), and biologically interrelated (dissolution rate) properties. The system first identifies the desirable properties for optimum compatibility with the drug, selects those excipients that have the required properties, and then recommends proportions based on the assumption that all tablet formulations comprise at least one binder, one disintegrant, and one lubricant. Other... 

This optimization method, which represents the mathematical techniques, is an extension of the classic method and was the first, to our knowledge, to be applied to a pharmaceutical formulation and processing problem. Fonner et al. [15] chose to apply this method to a tablet formulation and to consider two independent variables. The active ingredient, phenylpropanolamine HC1, was kept at a constant level, and the levels of disintegrant (corn starch) and lubricant (stearic acid) were selected as the independent variables, X and Xj. The dependent variables include tablet hardness, friability, volume, in vitro release rate, and urinary excretion rate in human subjects. 

Many immediate-release tablets or disintegrating dosages can be dissolved directiy as intact entities however, most formulations require some grinding or rongh crnshing to ensnre complete extraction in a timely fashion. 

When tablet formulations are made, usually different quality criteria have to be met, e.g., a high crushing strength, a low disintegration time, a pre-set dissolution profile. A tablet consists normally of the pharmacon (the pharmacologically active compound the drug) and excipients. Hence, a tablet can be made with different relative amounts of excipients (a mixture composition) and this creates room for optimizing a tablet... 

To motivate the response surface approach, suppose that there is some response of interest (for example, crushing strength in the tablet formulation example of Section 2.1.1), and a set of quantitative, continuous design variables that are of interest to the researcher (for example, the quantities of glidant, lactose, and disintegrant for the tablet formulation example). One possible objective for the researcher might be to understand and describe the relationship between the design variables and the response. This relationship can be described mathematically by... 

When speaking about the optimisation of a (tablet) formulation then in most cases the attainment of preferable response values is meant, e.g. a high crushing strength, a low disintegration time, a certain dissolution profile etc. Another important desirable property of a formulation can be that the formulation is robust towards (small) deviations (errors) in process conditions or the proportions of the excipients this means that despite these errors the values of the responses considered remain at (almost) the same level or deviate with only an acceptable amount. It is of course desirable to maintain properties of any product on exactly the same value during production or use, but on the other hand this can be very expensive... 

Many papers have been published in which an experimental design is used to optimize tablet formulations. Both process variables as well as compositional variables (quantitative and qualitative) were used as independent (adjustable) variables. The studied dependent variables (factors to be optimized) are physical tablet properties directly after preparation such as weight variation, crushing strength, dissolution profile, disintegration time and friability. Doombos reviewed papers in which statistical methods were used to optimize tablet formulations [13]. 

Since the aim of this study was to evaluate the use of the change in the tablet properties during storage as a parameter to express the physical stability of tablet formulations, the Storage to Initial Ratio of the crushing strength (SIR(S)) and of the disintegration time (SIR(D)) were calculated and used as response values for equation (2). The calculations of SIR(S) and SIR(D) were performed as in equation (1). The mean of the measurements directly after preparation were used as initial value. 

Since the SIR of disintegration time after storage depends on the compression load as well as on the disintegrant concentration, these factors should both be taken into account, when the SIR of disintegration time is used as a measure for the physical stability of tablets after storage, in the developing stage of tablet formulations. 

In this section a study is described in which tablets prepared with binary blends of a filler-binder and a disintegrant are evaluated, with respect to their physical stability after storage under tropical conditions. With the results of this study a selection from the excipients can be made, which are suitable for use in tropical countries. Tablet formulations can be developed with the thus selected excipients. 

Although the non-heated tablets did not disintegrate, they did partially split on their horizontal axis after a few minutes in the dissolution medium. In contrast, the thermally treated tablets remained totally intact. This splitting phenomenon of the non-thermally treated tablets increased the surface area of the tablet which could contribute to the more rapid dissolution rate of drug as compared with the thermally treated tablets. The tablet formulation also contains 60%... 

A tablet formulation is a complex system that contains the drug substance, usually a hydrophilic Lllersuch as lactose, a disintegrant such as cornstarch, a lubricant such as magnesium stearate, and maybe a Low-regulating excipient such as silicium dioxide (A sliilnfortunately, the quality... 

Lubrication is an important unit operation in manufacturing solid oral dosage forms, particularly when using a direct compression platform. Pharmaceutical lubricants can have a significant impact on product performance (e.g., disintegration and dissolution) as well as manufacturability. Lubrication is one of the most critical aspects of a tablet formulation. A lubricant is intended to reduce the friction between the tablet surface and die wall during and after compaction to enable easy ejection of the tablet. In low-dose dmg product development, three issues are associated with lubricating a direct compression formulation ... 

Microcrystalline cellulose (Avicel) is purified partially depolymerized cellulose, prepared by treating a-cellulose with mineral acids. In addition to being used as a filler, it is also used as dry binder and disintegrant in tablet formulations. Depending on the preparation conditions, it can be produced with a variety of technical specifications depending on particle size and crystallinity. It is often used as an excipient in direct compression formulations but can also be incorporated as a diluent for tablets prepared by wet granulation, as a filler for capsules and for the production of spheres. 

DuraSolv is Cima s second-generation fast-dissolving/disintegrating tablet formulation and is also produced using direct compression but using higher compaction... 

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