Please find the below possibility of the factor to increase Dissolution.
Factor Affecting on Dissolution Process
 Factors Relating To The Physicochemical Properties Of The Drug
The solid-phase characteristics of drugs, such as amorphicity and crystallinity, have been shown to have a significant effect or the dissolution rate. studies have demonstrated that the amorphous form of a drug usually exhibits greater solubility and higher dissolution rate as compared to that exhibited by the crystalline form, Piccolo and Saks3. showed that the dissolution rate of amorphous erythromy¬cin estolate is markedly lower than the crystalline form of erythromycin esto¬late, as exemplified.
The polymorphic forms of drugs have shown to influence changes in the solubilizing characteristics and thus the dissolution rate of the drug substance. Numerous reports have shown that polymorphism and the states of hydration, salvation, and/or complexation markedly influence the dissolution characteristics of the drug.
Coprecipitation andlor Complexation
Numerous reports have shown that polymorphism and the states of hydration, salvation, and/or complexation markedly influence the dissolution characteristics of the drug.
Radical CharacteristicsAccording to Nernst–Brunner theory, the dissolution rate is directly propor¬tional to the surface area of the drug. Since the surface area increases with decreasing particle size, higher dissolution rates may be achieved through the reduction of particle size. This effect has been highlighted by the superior dis¬solution rate observed after micronization of certain sparingly soluble drugs as opposed to the regularly milled form.
 Factors related to drug product formulation
A variety of factors concerning the formulation of a drug product can directly influence the dissolution rate of the active ingredient contained within it. Once these factors are completely characterized, one can use this information to achieve custom-tailored drug dissolution profiles. This information is then employed in the development of optimally effective dosage forms.
Excipients and Additives
Most solid dosage forms incorporate more than one excipient for various pur¬poses together with the active ingredient21 in the formulation. It has been shown that the dissolution rate of a pure drug can be altered significantly when mixed with various adjuncts. These adjuncts include diluents, binders, lubricants, granulating agents, disintegrants, and so on. In the following discussion we address the influence of excipients on the rate of dissolution of the active ingredient from a dosage form.
Several investigators have concluded that in most instances, reduction in parti¬cle size of drugs contained in tablets or capsules will enhance dissolution and absorption. This can most likely be attributed to the procedures22 employed in tablet production: that is, mixing the drug with usually hydrophilic diluents and subsequent granulation will result in a more hydrophilic surface, even for originally hydrophobic drug particles. Finholt et al.25,26. have extensively evaluated the effect of particle size on the dissolution rate of drug from granules and tablets. Figures illustrate this phenomenon with phenacetin and phenobarbital as the test compounds. Several other investigators have reported similar results26,20,27.28.
Granulating agent and binder
It has been reported by several investigators that binder and granulating agent incorporated in tablet formulation and other solid dosage forms can markedly influence the dissolution characteristics of the drug from the dosage form. Solvong and finholt19 have shown that Phenobarbital tablet granulated with gelatin solution provide a faster dissolution rate in human gastric juice than do those prepared using sodium carboxy methylcellulose or polyethylene glycol 6000 as binder.
Several reports have been published in the literature demonstrating the effect of various disintegrating agents on the dissolution rate of tablets27-29. It must be noted that the type and amount of disintegrating agent employed in the formulation significantly controls the overall rate of dissolution of the dosage form.
Lubricants that are commonly incorporated in the formulation of solid dosage forms fall predominantly in the class of hydrophobic compounds. Conse¬quently, the nature, quality, and quantity of the lubricant added can affect the dissolution rate.
The effects of various lubricants on the dissolution rate of salicylic acid tablets were studied by Levy and Gumtow30. They concluded that mag¬nesium stearate, a hydrophobic lubricant, tends to retard the dissolution rate of salicylic acid tablets, whereas sodium lauryl sulfate enhances dissolution, due to its hydrophilic character combined with surface activity, which increases the microenvironment pH surrounding the weak acid and increases wetting and better solvent penetration into the tablets.
Interfacial tension between drug and dissolution medium
The properties of the interface between the drug and the dissolution medium can become a deciding factor as far as dissolution rate is concerned. The characteristics can be modified by the addition of agent that act at the interface.
The drugs that are practically insoluble in aqueous medium (<0.01%) are of increasing therapeutic interest, particularly due to the problems associated with their bioavaibility when administered orally. Drugs with low solubilities when incorporated with surfactants can enhance their dissolution rate.
 Factor related to the dissolution testing device
Eccentricity of Agitating (Stirring) Element
The current official compendium specifies that the stirring shaft must rotate smoothly without significant wobble. The lerrd significant gives the experi¬menter full right to ensure that such wobble does not significantly affect the dissolution rate. Additionally, USP XX/NF XV states that the axis of rotation of the stirring shaft must not deviate > 2 mm from the axis of the stirring vessel. This implies that this specification permits eccentricity up to ±2 nun but that such eccentricity must not significantly affect the dissolution rate. This is certainly an excessive amount.
The speed of the rotational device selected by official compendium is 100 rpm. Other speeds are specified for certain drugs. Precise speed control is best obtained with a synchronous motor that locks into line frequency25. Such motors are not only more rugged but are far from reliable. Periodic variations in rpm might result in possible disturbance in rotational acceleration. This phenomenon, present in almost all rotational devices, is commonly referred to as torsional vibration, Such vibration indicates a variation in the velocity of rotation for short periods of time. There average velocity was well within ±4% of the specified rate.)
Vibration is a common variable introduced into a dissolution system due to various causes. It can effect change in the flow patterns of the dissolution medium. Additionally, it can introduce unwanted energy to the dynamic sys¬tem. Both effects may result in significant changes in dissolution ratel-8.
It can be stated with a significant amount of certainty that the degree of agita¬tion, or the stirring conditions, is one of the most important variables to consider in dissolution. Given the background on the various theories of disso¬lution, it is apparent that agitation conditions can markedly affect diffusion-controlled dissolution, because the thickness of the diffusion layer is inversely proportional to agitation speed. Wurster and Taylor39 employed the empiritical relationship.
K = a(N)b
where N is the agitation rate, K the reaction (dissolution) rate, and a and b arc constants. For diffusion-controlled processes, b = I. Dissolution that is interfacial-reaction-rate-controlled will he independent of agitation intensity and thus b =0.
Flow Pattern Disturbances
For dissolution-rate data to be reproducible and reliable, the flow pattern should be consistent from test to test. The geometry and alignment of the stir-ring device, external vibration, and rotational speed are some of the factors that can influence flow patterns. In 1978, DRTL conducted an extensive exam¬ination of these factors and their influence on dissolution testingl0. They concluded that the geometry of the rotating paddle and/or basket, the flask dimensions, and the sampling positions can all introduce various types of flow patterns that can alter the dissolution characteristics of the drug product. Cox at al.29 further suggested that variations in smoothness of the round-bottomed flask can make significant differences in flow patterns as well. The influence on flow patterns of the vertical distance of the basket or pad¬dle from the lowest point of the bottom of the round-bottomed flask should also be considered. The official compendium specifies this distance to be 2.5 cm (±2 mm).
Sampling Probes, Position, and Filters
Large probe can affect the hydrodynamics of the system and therefore the dissolution rate of some dosage forms, causing results that differ from those obtained by manual sampling30-35. USP/NF states that samples should be removed at approximately half the distance from the bottom of the basket or paddle to the surface of the dissolu¬tion medium and not closer than 1 cm to the side of the flask. The choice of a filter should he preceded by an investigation of the adsorption characteristics of the drug and the particular filter material.
Factors related to dissolution test parameters
USP/NF specifics that the dissolution medium must be held at 37°C ( 0.5°). Although most commercial water baths can meet this standard of performance, failure to meet this requirement is not uncommon, It is often assumed that the water-bath temperature and the flask temperature are the same. Plastic flasks have a heat transfer coefficient approximately 3.5 times less than that of glass M. As the temperature difference between the bath and the flask’s medium is lowered, the amount of heat transferred into the flasks is reduced. It is vital to cover the flasks at least during dissolution testing.
Since the drug solubility is temperature dependent, its careful control dur¬ing the dissolution process is crucial. The effect of temperature variations of the dissolution medium depends mainly on the temperature-solubility curves of the drug and excipients in the formulation. Stokes’ equation36 explains the temperature dependency of a dissolved molecule and diffusion coefficient:
Where, k is the Boltzmann constant and the denominator expresses the Stokes force for a spherical molecule, n is the viscosity, and r is the radius of the molecule.
The constituents, nature, and overall characteristics of the dissolution medium have a significant bearing on the dissolution performance of a drug substance. Also, selection of the proper dissolution medium for dissolution testing depends on the solubility of the drug as well as on economics and practicality. Factors such as dissolved gases, media pH, and viscosity of the medium have been shown to be significantly influential as far as dissolution rate is con¬cerned.
Dissolution rate decrease with increase viscosity of the dissolution medium; especially in the case of diffusion controlled dissolution process. viscosity has very little effect on interfacial controlled dissolution process.
1.4.5 Miscellaneous factor
The relative density of the tablets was found to decrease, resulting in increased disintegration time with increase in water sorption-rate constants.
In relation to the dissolution rate of a drug substance, humidity is usually asso¬ciated with storage effects. Moisture has been shown to influence the dissolu¬tion of many drugs from solid dosage forms6,29,38. Taborsky-Urdinola et al.30 reported decreases in the dissolution of prednisone tablets exposed to the environment with varying degrees of relative humidity. Hanson and Hanson38 found that three of the four formulations of prednisone tablets showed drastic decreases in dissolution rate when the tablets were exposed to high humidity. Gupta and Gupta39, however, did not find significant changes in dissolution behavior of two drugs, except weight gain. The environmental conditions to which the dosage forms are exposed, moisture content in particular, should be rigorously assessed if reproducible and reliable dissolution data are to be obtained. Additionally, humidity during the manufac¬ture of the dosage form should be carefully controlled to guarantee the quality of the product from batch to batch.
Analytical methods be checked carefully for each dissolution system. Extreme care must also be exercised when laboratory methods are introduced into quality control to ensure that no part of the equipment interferes with sensitive determinations.
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