MINISTRY OF HEALTH OF THE RUSSIAN FEDERATION
Содержимое (Table of Contents)
Solutions are a liquid dosage form obtained by dissolving liquid, solid or gaseous substances in an appropriate solvent or a mixture of intermixing solvents to form homogeneous disperse systems.
This monograph does not apply to solutions for ophthalmic, parenteral and inhalation use.
Solutions for parenteral administration should comply with the requirements of the GM «Parenteral dosage forms»; solutions for ophthalmic administration — the requirements of the GM «Ophthalmic dosage forms»; solutions for inhalation administration — the requirements of the GM «Dosage forms for inhalation.»
The solutions include the following dosage forms:
- solutions themselves,
- aromatic waters,
- concentrates for solutions.
By the route of administration solutions are classified into solutions for oral administration, external use and topical application.
Depending on the solvent nature, the solutions are divided into aqueous and non-aqueous solutions.
Solutions for oral administration, for external use and topical application are solutions containing one or more active ingredients in a suitable solvent or consisting only of liquid substances for oral administration; application to the skin; application to mucous membranes and for irrigation of body cavities, respectively.
Drops are a liquid dosage form containing one or more active ingredients dissolved or dispersed in an appropriate solvent and dosed by drops with a special device (dropper, pipette, etc.).
Mixtures is a liquid dosage form, predominantly extemporary, for oral administration and dosed with spoons. Dry mixtures are diluted with water up to the required volume before use.
Aromatic water is aqueous or hydroalcoholic solutions saturated with essential oil components.
Syrups are a liquid dosage form which is predominantly a concentrated solution of various sugars containing the active ingredients and excipients.
Concentrates for solutions are liquid dosage forms of high concentration, for producing solutions by subsequent dilution.
Solutions can be obtained from concentrates and solid dosage forms (powders, tablets, granules, lyophilizates, etc.). Standard pharmacopoeia solutions are the type of concentrated solutions, which are aqueous or alcoholic solutions of certain active ingredients (industrial production) of a strictly defined concentration specified in the relevant monographs or regulatory documentation.
The content of active ingredients in solution is expressed as a percentage concentration (weight and volume, weight or volume). When producing solutions, a weight-volume method of production is used.
Aqueous solutions are produced by dissolving the active ingredients and excipients in a suitable solvent, most often in purified water, diluting concentrates or standard pharmacopoeia solutions.
Water and aqueous solutions close in density to water are measured, solid pharmaceutical substances are weighed. Solvents and solutions, the density of which is more or less than 1.0, are weighed.
When producing solutions of high-molecular compounds, the nature of the substance is taken into account. Solutions of unlimited swelling high-molecular compounds (pepsin, trypsin, etc.) are produced according to the general rules for solution production. Dissolution of limited swelling high-molecular compounds (gelatin, starch, methylcellulose, etc.) should be performed, as a rule, under certain conditions, which promote their preliminary swelling and subsequent dissolution. At the swelling stage these conditions provide for a certain amount of solvent, temperature, swelling time and compliance with the conditions that allow the swollen high-molecular compounds to pass into the solution (heating or cooling).
For producing solutions of colloidal compounds (protargol, collargol) additional technological operations are used to ensure the hydration of colloidal particles.
When producing oil solutions, heating is used to increase the dissolution rate of the active ingredients and excipients.
The technology of alcohol solutions does not imply heating. The main solvent is 96% alcohol, which, if necessary, is diluted with water to the required concentration.
Aromatic waters are produced in several ways: distillation of essential oil herbal medicinal raw materials with water vapor, dissolution of essential oil in water or dilution of concentrates. To increase the stability of aromatic waters, 96% alcohol may be added to their composition.
Solvents for solutions are selected based on the properties and nature of the active ingredient(s) to ensure that there is no possible chemical, physical and chemical interaction between the solvent and the active ingredient(s). The solvent should not affect the pharmacological activity of the active ingredient(s).
Purified water is used as the main solvent for aqueous solutions for oral administration, external use or topical application. In non-aqueous solutions, the main solvents are ethyl alcohol of various concentrations, fatty oils, liquid paraffin, glycerin, etc.
In the manufacturing/producing of solutions, suitable antimicrobial preservatives, antioxidants, stabilizers, solubilizers, co-solvents and flavoring agents approved for medical use can be added to their composition.
Excipients should not adversely affect the labelled therapeutic effect of the medicinal product, in the concentrations used they should not cause local irritation.
Solutions should comply with the requirements of the GM «Dosage forms» and pass the tests for the following quality attributes:
- «Deliverable volume» (for solutions for parenteral administration and solutions for oral administration) or «Container contents volume», Syrups should comply with the requirements of the GM «Syrups».
In addition, aqueous solutions and 96% alcohol-based solutions are monitored for «pH, Acidity or Alkalinity» parameter, non-aqueous solutions are monitored for «Density», solutions of high-molecular compounds — for «Viscosity» parameter, oil solutions — for «Acidity number «and» Peroxide number» parameters.
The control over the parameter «Ethyl alcohol» is carried out for alcohol solutions produced using ethyl alcohol with a concentration below 40% as a solvent in accordance with the requirements of the GM «Determination of ethyl alcohol in liquid pharmaceuticals», at a concentration above 40%, the quality attribute «Density» is controlled.
The quality attribute «Deliverable volume» is determined for solutions for parenteral administration and solutions for oral administration, for other solutions the indicator «Container contents volume» is determined.
If necessary, solutions are monitored for the parameters «Transparency», «Color», «Sterility» in accordance with the requirements of the monograph or regulatory documentation.
Tests are carried out in accordance with the requirements of the relevant GM for the methods of analysis.
The pH is determined, if specified in the monograph or regulatory documentation, and an acceptable range of pH values is registered. The test is carried out by a potentiometric method in accordance with the requirements of the GM «Ionometry».
When determining the acidity or alkalinity limits of solutions using indicators, acid or alkaline solutions with a concentration of 0.01 to 0.1 M are used.
In accordance with the requirements of the GM «Dosage forms».
In accordance with the requirements of the GM «Dosage forms».
In accordance with the requirements of the GM «Storage of medicinal products». In a package that provides stability during the labelled shelf life of the medicinal product in a place protected from light in the conditions stipulated by the monograph or regulatory documentation.