R & D

As it is known there are a lot of different dosage forms of drugs. And one substance may be given different variants of dosage forms for any administration routes taking into account the goals and the presence of certain pathology.

Application sphere of different dosage forms

There are four groups of dosage forms (classification by the state of aggregation):

• solid;
• soft;
• liquid;
• gaseous.

Development of dosage forms for each drug is performed taking into account physical and chemical properties of the active substance and the disease, for the treatment of which the medicine is intended. So, for example, soft dosage forms are usually used locally for application to the skin and mucosa. An advantage is the absence of systemic action and therefore fewer adverse effects.

Development of tablets, capsules and other solid dosage forms is performed for drugs which are used for the treatment of the diseases of internal organs. Each medicine has a tropism to certain tissues, organs and systems: some substances are accumulated mostly in urinary system, others – in cardiovascular system and etc. These properties are given to the drugs artificially at the stage of development of dosage form that is aimed at increasing the bioavailability and therapeutic efficiency.

For the treatment of the pathologies of respiratory system the development of tablets and capsules is nowadays less preferable. Using gaseous dosage forms is optimal for increasing the bioavailability of the drug and decreasing the systemic actions. Although in some cases other administration routes are used and therefore production of the pilot batches of tablets and other dosage forms is constantly performed.

After the optimal dosage form has been determined and the composition of the excipients for the dosage form has been chosen, production of the pilot batches of tablets and other dosage forms is performed for their further investigations.

Development of finished pharmaceuticals

• development of the structure and technology of new dosage forms (synthetic pharmaceuticals and natural biologically active compounds) and their biopharmaceutical assessment;
• performance of dissolution test for various dosage forms: medicines of prolonged action, lipophilic pharmaceuticals in soft gelatinous capsules, transdermal systems of transfer, chewable tablets, lozenges;
• preclinical pharmacokinetics study of pharmaceuticals;
• conducting the analytical part of bioequivalence study.

Creation of new dosage forms including development of them:

• Solid dosage forms (tablets, granules, microgranules, spansule, dry extracts, lyophilized extract, pellets);
• Soft dosage forms (ointments, creams, gels, oleogel, pharmaceuticals in soft gelatinous capsules);
• Liquid dosage forms (tinctures, extracts, elixirs, solutions, suspensions, emulsions, microemulsions, oil extracts);
• Modified dosage forms;
• Creation of dosage forms with improved bioavailability by producing nanosystems (nanoemulsion, solid nanoparticulate delivery systems), liposomes, pellets, microcapsules;
• Creation of dosage forms with controlled release.

During the work the following stages are carried out:

• choice of the optimum composition of dosage form;
• biopharmaceutical assessment of dosage forms and substances in vitro: tests “Drug release”, “dissolution” accompanied by methods named “Basket”, “rotating blade”, “blade over a disk”, dialysis cell, etc.;
• modeling of in vitro systems: modeling of transdermal or oral applying, creation of simulated conditions to assess gastrointestinal drugs with controlled release, selection of dissolution media, use of the original two-phase system to evaluate the release of soft gelatin capsules with lipid matrix and lipophilic, water-insoluble substances;
• development or adoptation of method of quantitative determination of drug concentration in dissolution medium;
• validation of analytical method according to the requirements of State standard of the Russian Federation and USP;
• in vivo study of drug pharmacokinetics in a new dosage form at the stage of drug design;
• determination of correlation between in vitro and in vivo tests carried out in lipophilic, poorly soluble substances and the dosage forms on their basis;
• justification of quality indicators of finished product, development and validation of control methods of a dosage form;
•  study of stability of a developed dosage form in natural conditions and by the method of “accelerated aging”;

• creation of documentation (specification, technological instruction, laboratory regulations) on finished product;
• registration of scientific report.

Preclinical pharmacokinetics of drugs include:

• Design and planning a study;
• Conducting experiments on laboratory animals (mice, rats, rabbits, guinea pigs);
• Development of test procedures of biomaterial preparation and quantitative determination of an active substance and/or metabolites in plasma/urine/tissues and organs;
• Validation of analytical method according to the requirements of State standard of the Russian Federation and USP;
• Assessment of pharmacokinetic parameters at single and/or multiple administration, statistical processing of the data obtained;
• Registration of scientific report.

Assessment of bioequivalence includes:

• Development of test procedures of biomaterial preparation and quantitative determination of an active substance and/or metabolites in plasma/urine/tissues and organs;
• Validation of analytical method according to the requirements of State standard of the Russian Federation and USP;
• Calculation and statistical assessment of pharmacokinetic parameters;
• Registration of scientific report.