The history, current state and perspectives of aerosol therapy

Nebulization is a very effective method of drug administration. This technique has been popular since ancient times when inhalation of plants rich in tropane alkaloids with spasmolytic and analgesic effects was widely used. Undoubtedly, the invention of anasthesia in the 19th century had an influence on the development of this technique. It resulted in the search for devices that facilitated anasthesia such as pulveriser or hydronium. From the second half of the 21st century, when the first DPI and MDI inhalers were launched, the constant development of aerosol therapy has been noticed. This is due to the fact that nebulization, compared with other means of medicinal substance application (such as oral and intravenous routes of administration), is safer and it exhibits a positive dose/efficacy ratio connected to the reduction of the dose. It enables drugs administration through the lung and possesses very fast onset action. Therefore, various drugs prescribed in respiratory diseases (such as corticosteroids, β-agonists, anticholinergics) are present on the market in a form of an aerosol.

In Vivo Activity Of Medications In Different Dosage And Ultrahigh Dilutions

Biological activity of medical remedies varies depending on the dosage of the medicinal substance. As we analyze the results of the medicinal effect we can determine three areas of its effect. First of all, this is a therapeutic area where its dose-dependent medical effect is demonstrated. When a certain amount of drug in the body it exceeded this causes transition to the toxic area where every medicine causes certain pathological manifestations. Significant decrease of the drug dose demonstrates the area of no effect on the body. At the same time similar body reaction can be observed with homeopathic remedies in ultrahigh dilutions. Classical definition of a dose as an amount of substance introduced into the body is not suitable for homeopathic remedies that often don’t have drug substance molecules at all. The presence of areas of different reaction is explained by the effect of electromagnetic wave emissions of drug substances. It is known that molecules of all medicinal substances have certain frequencies that come into resonance with different body structures, including genes that have similar oscillatory characteristics. This causes expression of certain genes and increase of their activities. Increase of an allopathic substance dose causes voltage increase it its wave and consequently an increase of the effect on the genes. However overdose causes hyperstimulation and exhaustion of the gene under expression and consequently pathological symptoms develop. On the other hand a dose too small cannot stimulate gene activity and this causes a lack of medical effect. As demonstrated by long-term studies, the activity of potentiated remedies (in ultrahigh dilutions) is related to development of coherence. Coherence is a phasic shift of the medicinal wave that occurs with potentiation of a remedy. As the potency is increased, every step, i.e. coherent wave shift decreases, thus increasing the probability of exact coincidence of the drug and gene waves and their contraposition to the wave of a xenobiotic. Wave shift by have the phase of a xenobiotic wave makes them opposite in terms of amplitude. They begin to damp each other and thus pathogenic effects of a xenobiotic are neutralized. In such a way, drug activity on the body is determined by wave characteristics of the medicinal substance molecules. Activity of allopathic medications depends on the dose, e.g. the number of drug substance molecules. Activity of homeopathic medications depends on the degree of their potentiation.

4D Investigation of Vortex Fluid Motion Inside the Eyeball

The eye is a complex system of boundaries and fluids with different viscosities within the boundaries. At present, there are no experimental possibilities to thoroughly observe the dynamic 4D processes after one or another method of eye treatment is applied. The complexity of cumulative, i.e., focusing, and dissipative, i.e., scattering, convective and diffusion 4D fluxes of fluids in the eye requires 4D analytical and numerical models of fluid transfer in the human eyeball to be developed. The purpose of the study was to develop and then verify a numerical model of 4D cumulative-dissipative processes of fluid transfer in the eyeball. The study was the first to numerically evaluate the values of the characteristic time of the drug substance in the vitreous cavity until it is completely washed out, depending on the injection site; to visualize the paths of the vortex motion of the drug in the vitreous cavity; to determine the main parameters of the 4D fluid flows of the medicinal substance in the vitreous cavity, depending on the presence or absence of vitreous detachment from the wall of the posterior chamber of the eye. The results obtained are verified by the experimental data available to doctors. In the eye, as a partially open cumulative-dissipative system, Euler regions with high rates of cumulative flows and regions with low speeds or stagnant Lagrange flow zones are defined

New approaches to the design of analgesic medicinal substances

A gamma-pyrone derivative, comenic acid, activates the opioid-like receptor-mediated signaling pathway that modulates the NaV1.8 channels in the primary sensory neuron membrane. These channels are responsible for generation of the nociceptive signal; gamma-pyrones can therefore have a great therapeutic potential as analgesics, and this effect deserves a deeper understanding. The novelty of our approach to the design of a medicinal substance is based on a combination of the data obtained on living neurons using very sensitive physiological methods and the results of quantum-chemical calculations. This approach allows to correlate the molecular structure of gamma-pyrones with their ability to evoke a physiological response of the neuron. Comenic acid can bind two calcium cations. One of them is chelated by the carbonyl and the hydroxyl functional groups, while another one forms the salt bond with the carboxylate anion. Calcium-bound gamma-pyrones are fundamentally different in electrostatic properties from the free gamma-pyrone molecules. These two calcium ions are the key elements involved in ligand-receptor binding. It is very likely ion-ionic interactions between these cations and anionic functional groups of the opioid-like receptor that activate the latter. The calculated intercationic distance of 9.5 Å is a structural criterion for effective ligand-receptor binding of calcium-bound gamma-pyrones.

PerspectivesRe-legalizing cannabis for medical use in the USA

Background The purpose of this paper is to discuss the history of cannabis, its benefits, risks and the federal re-legalization of cannabis for medical use in the USA. Methods Thirty-six states have legalized cannabis as a medicinal substance. Cannabis is a Schedule I drug, an illegal and controlled substance, making research on the substance challenging. Both the American Medical Association and the American Nurses Association have called for the re-scheduling of marijuana, so that research can be conducted, its benefits and risks discovered. Results Data are demonstrating that medical marijuana may be beneficial as a step-down drug, decreasing the use of opioids and benzodiazepines, as well as deaths related to their overdose. Studies have indicated that cannabis is a low-risk substance, when compared to alcohol and opioids. There appear to be specific conditions in which cannabis provides relief of symptoms which no other medications can provide. There is also evidence of cannabis’s negative effects on the developing brain. Conclusion Cannabis should be rescheduled and researched, so that its risks and benefits can be identified. Its medicinal use should be monitored, and its availability protected in children, pregnant women and pets.

A most convenient and patient compliance dosage form- Tablet

Tablet is defined as solid pharmaceutical dosage form containing drug substance generally with suitable diluents and prepared by either compression which is given as a single unit and are known as solid unit dosage form. Tablets remain popular as a dosage form because of the advantages afforded, both to the manufacturer (e.g. simplicity and economy of the preparation, stability, and convenience in packing, shipping and dispensing) and the patient. The excipients include diluents, Binders and adhesives, disintegrates, etc. Tablets vary in shape and differ greatly in size and weight depending on the amount of the medicinal substance. The ingredients must be granulated prior to compression to assure an even distribution of the active compound in the final tablet. There are two basic techniques which can be used to granulate powders for compressions into a tablet are wet granulation and dry granulation. In this review article tablet manufacturing and evaluation have been discussed. Keywords- Tablet, Granulation, Picking and sticking, Dissolution test, weight variation

Suppository Solid Provision Technology

Suppository can be used for systemic effects in conditions where oral drug preparations will not be resistant or absorbed rapidly. Once inserted the base suppository melts, softens or dissolves causing the underlying medicinal substance to enter the tissues of the area. In the manufacture of suppositories, there is a term known as the exchange rate for making oleum cacao based. Therefore, weighing should not be carried out one by one, but the exchange rate of active substances is calculated to find the required oleum cacao. The advantage of weighing the ingredients is to provide the suppository period at the time of printing.

Modern polymers in prolonged release tablet technology

Currently, the delivery systems of second and third generation are of particular interest among pharmaceutical forms. Second generation pharmaceutical forms include systems with prolonged release of the active substance, third generation pharmaceutical forms include systems with controlled release. A slow continuous release of a medicinal substance may be achieved by using special excipients or by using special technologies. For the production of tablets with prolonged release, the most common are special excipients, namely, polymers and their compositions. The use of polymers as carriers of pharmaceutical substances used to program the kinetic frequency and location of the release is known since the middle of XX century [9]. To date, significant progress has been made in the use of polymers to prolong the release: the influence and interaction of polymers and drugs have been studied, the mechanisms of drug release have been studied, ways of programming release kinetics using various properties of polymers, etc. In the article the modern state in the field of technology of tablets with prolonged release is considered. Advantages of prolonged release, mathematical models for description of drug forms with prolonged release are described. Technologies of tablets with prolonged release, types of delivery systems and mechanisms of release of an active pharmaceutical ingredient are considered. The article presents modern polymers that are used in the technology of tablets with prolonged release. The classification of polymers in relation to water and to physiological liquids is presented.

Experimental Investigation of Immunomodulator Galavit® Diffusion in a Model System

Introduction. The widespread use of immunomodulators in medical practice contributes to the development of their new dosage forms.Aim. The aim of this work is to develop a transdermal therapeutic system (TTS) Galavit® and to study a diffusion of the drug from it through the Strat-M membrane in vitro.Materials and methods. The medicinal substance was Galavit® in the form of a powder for the preparation of a solution for intramuscular administration («SELVIM», Russia). Saline solution, sodium dodecyl sulfate, apricot kernel oil, Decaglyn PR-20 and others were used as excipients. Heidolph DIAX900 dispersant (Germany) and ultrasonic homogenizer Heilscher UIS250V (Germany) were used to make the emulsion compositions. The delamination time and particle size of emulsion compositions were determined using the LUMiSizer dispersion analyzer (LUM, Germany). Diffusion studies of Galavit® from TTS through the Strat-M membrane (25 mm in diameter, Merck Millipore) were carried out on the Copley diffusion analyzer (UK). Quantitative determination of Galavit® was performed by spectrophotometry (UV-2600 Shimadzu, Japan) in the wavelength range 294–298 nm in model media.Results and discussion. The characteristic parameters of emulsion compositions were determined during the study: the particle size varied from 0.1 to 2 µm, the delamination time – from 9 to 95 min depending on the composition. The maximum yield of the drug from the TTS was 30 % through the membrane.Conclusion. The possibility of transdermal transfer of Galavit® from TTS is shown in model experiments.