Drug release particle size influence

The majority of commercially available matrix formulations are in the form of tablets, and although developing them may initially seem simple, the formulation scientist is required to consider a number of variables that influence drug release, as well as the manufacturing and processing of these tablets. The release rate from the matrices is dependent upon drug characteristics particle size, solubility and dose, release controlling polymers type, level and particle size, fillers type and level, tablet properties porosity, tortuosity (affected by compression force) and shape [13-35],... 

Several in vitro tests are currently employed to assure drug product quality. These include purity, potency, assay, content uniformity, and dissolution specifications. For a pharmaceutical product to be consistently effective, it must meet all of its quality test criteria. When used as a QC test, the in vitro dissolution test provides information for marketing authorization. The dissolution test forms the basis for setting specifications (test, methodology, acceptance criteria) to allow batch release into the market place. Dissolution tests also provides a useful check on a number of physical characteristics, including particle size distribution, crystal form, etc., which may be influenced by the manufacturing procedure. In vitro dissolution tests and QC specifications should be based on the in vitro performance of the test batches used in in vivo studies or on suitable compendial specifications. For conventional-release products, a single-point dissolution... 

The factors influencing the release of drugs from hydrophilic matrices include viscosity of the polymer, ratio of the polymer to drug, mixtures of polymers, compression pressure, thickness of the tablet, particle size, pH of the matrix, entrapped air in the tablet, solubility of the drug, the presence of excipients or additives, and the mode of incorporation of these substances. 

H. Velasco, M. V., Ford, J. L., Rowe, P., and Rajabi-Siahboomi,A. R. (1999), Influence of drug hydroxypropylmethylcellulose ratio, drug and polymer particle size and compression force on the release of diclofenac sodium from HPMC tablets, I. Controlled Release, 57, 75-85. 

Ragnarsson, G., Sandberg, A., Johansson, M. O., Lindstedt, B., and Sjoegren, J. (1992), In vitro release characteristics of a membrane-coated pellet formulation. Influence of drug solubility and particle size, Int. J. Ph+arm., 79, 223-232. 

The physical characteristics of final dosage forms such as texture (porosity and surface area) and particle size distribution can affect the dissolution rate, and therefore the bioavailability of the product. It is common to see an increase in particle size when scaling up, therefore to anticipate the in vitro release profiles for a Spray Dried Drug Product (SDDP) manufactured at a larger scale, we have evaluated the influence of particle size and texture on dissolution in the case of a laboratory scale SDDP. 

Another issue is reproducibility. The formulation may work perfectly in an in vitro test system, but the dosage form requires aerosolization, and lung deposition is a function of the characteristics of the aerosol (dose, mass concentration, droplet/particle size, etc.) and the nature of the inspiratory maneuver, a factor that the patient has control over. These factors can influence performance to a far greater extent than can be built into a particle, and thus the term controlled does not seem a defensible objective for pulmonary delivery. The vagaries of the deposition profile and of the amount that will deposit also imply that sustaining a certain drug concentration is a difficult proposition, but the loosest definition extended release, seems an acceptable goal within the boundaries set by the clearance mechanisms. 

For poorly soluble drugs, particle size of the drug has a major influence on its release profile [47 9], A decrease in particle size of the drug causes increase in solubility and hence faster drug release rate. 

The release of drug from suppository bases is known to be influenced by various factors such as drug-vehicle interactions, vehicle composition, solubility and particle size of drug in vehicle (18). 

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