Drug formulations solution concentrations

Mechanisms of dissolution kinetics of crystals have been intensively studied in the pharmaceutical domain, because the rate of dissolution affects the bioavailability of drug crystals. Many efforts have been made to describe the crystal dissolution behavior. A variety of empirical or semi-empirical models have been used to describe drug dissolution or release from formulations [1-6]. Noyes and Whitney published the first quantitative study of the dissolution process in 1897 [7]. They found that the dissolution process is diffusion controlled and involves no chemical reaction. The Noyes-Whitney equation simply states that the dissolution rate is directly proportional to the difference between the solubility and the solution concentration ... 

The law of 1906 was only a beginning. It did not regulate the safety and effectiveness of drug formulations. This was no more evident than in the case of mass poisoning which resulted from the consumption of "elixir of sulfanilamide" produced by the S.E. Massengill Company of Bristol, Tennessee. Between September and October 1937 doctors had prescribed almost 12 gallons of a 10% solution of sulfanilamide in an ethylene glycol(antifreeze) solvent flavored with saccharin, caramel, amaranth, and raspberry extract. The company s chief chemist, Harold Watkins, was not aware of the toxicity of that concentration of the solvent. 

Recently, a new class of inhibitors (nonionic polymer surfactants) was identified as promising agents for drug formulations. These compounds are two- or three-block copolymers arranged in a linear ABA or AB structure. The A block is a hydrophilic polyethylene oxide) chain. The B block can be a hydrophobic lipid (in copolymers BRIJs, MYRJs, Tritons, Tweens, and Chremophor) or a poly(propylene oxide) chain (in copolymers Pluronics [BASF Corp., N.J., USA] and CRL-1606). Pluronic block copolymers with various numbers of hydrophilic EO (,n) and hydrophobic PO (in) units are characterized by distinct hydrophilic-lipophilic balance (HLB). Due to their amphiphilic character these copolymers display surfactant properties including ability to interact with hydrophobic surfaces and biological membranes. In aqueous solutions with concentrations above the CMC, these copolymers self-assemble into micelles. 

Nebulizers are devices for converting aqueous solutions or micronized suspensions of drag into an aerosol for inhalation, although the drug formulations are, wherever possible, aqueous solutions. Selection of appropriate salts and pH adjustment will usually permit the desired concentration to be achieved. If this is... 

The irradiation of micellar solutions effects the phase behavior and the critical micelle concentration (CMC). Because radiation sterilization of biopharmaceutical products is a common routine it is important to investigate the influence of radiation on surfactants that are widely used in the pharmaceutical industry for formulations as wetting agents, emulsifiers, or solubilizers. In particular, in drug formulations... 

To enhance corneal drug absorption, the tear film concentration can be prolonged by manually blocking the nasolacrimal ducts or by tilting the head back to reduce drainage (see Chapter 3). Another effective technique to increase corneal penetration is to administer a series of ophthalmic solutions at intervals of approximately 10 minutes. It has been determined, however, that when different drug formulations are given as drops in rapid succession, the medications first applied are diluted and do not achieve fiill therapeutic potential. 

Providing the product is reconstituted in a small volume of diluent, the resulting solution is more concentrated than the formulated solution before freeze-drying. It is therefore easier to assay minute amounts of drug or impurities and the analytical methods used for QC release can be implemented. 

Thus, the required %v/v propylene glycol is (27.1/ 46.5) X 100 = 58.3. Alternatively, the %v/v of the new cosolvent can be solved using an algebraic method involving the solution of simultaneous equations however, aligation is a simpler method when more than one cosolvent is to be included in the formulation. When a vehicle is to be formulated for the first time, it is necessary to experimentally determine the concentration of some cosolvent necessary to maintain the required concentration of drug in solution. This value can then be used to calculate the ADR and the final vehicle calculated as illustrated previously. 

With some molecules, a high concentration results in a lamellar phase, but no additional mesophases are formed if the concentration is reduced. The lamellar phase is dispersed in the form of concentric-layered particles in an excess of solvent (water or aqueous solution). This results in a vesicular dispersion. If the mesogenic material consists of phospholipids, the vesicular dispersion is called a liposomal dispersion. In principle, liposomes may be dispersed in oily continuous media too. However, the latter systems are of minor interest in drug formulation. 

For compounds possessing a low aqueous solubility, there are several approaches that can be used to enhance the concentration of drug in solution. Many drugs are weak bases or acids and can be formulated as water-soluble, pharmaceutically acceptable salts. Ideally, salt... 

Tetrakis(4-A, A -dimethylaminobenzene)porphyrinato-manganese(III) acetate was used as a novel carrier for a selective iodide ion electrode (Farhadi et al, 2004). The sensor exhibited not only excellent selectivity to iodide ion compared to Cl and lipophilic anions such as CIO4 and salicylate, but also a Nernstian response for iodide ion over a wide concentration range from 1.0 X 10 to 7.5 X 10 mol-l h The potentiometric response was independent of the pH of the solution in the pH range 2-8. The electrode could be used for at least 2 months without any considerable divergence in the potential. The electrode was applied to the determination of iodide in seawater samples and drug formulations. 

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