Conceptual Importance of Medicinal gases for its Significance in Pharmaceuticals

 

Farheen Fatima Ahsan1, Afreen Fatima1, Nuha Rasheed2*, Abdul Saleem Mohammad3

1Department of Pharma. D, Nizam Institute of Pharmacy, Deshmukhi (V), Pochampally (M),

Behind Mount Opera, Yadadri (Dist)-508284, Telangana, India.

2Department of Pharmaceutics, Nizam Institute of Pharmacy, Deshmukhi (V), Pochampally (M),

Behind Mount Opera, Yadadri (Dist)-508284, Telangana, India.

3Department of Pharmaceutical Analysis and Quality Assurance, Nizam Institute of Pharmacy, Deshmukhi (V), Pochampally (M), Behind Mount Opera, Yadadri (Dist)-508284, Telangana, India.

*Corresponding Author E-mail: mohdsaleempharma@gmail.com

 

ABSTRACT:

The present review is on various medicinal gases that are very commonly used in anaesthesia and intensive cares that include nitric oxide, heliox, carbon dioxide, entonox, medical air, nitrous oxide, oxygen.etc. The conceptual importance of medicinal gases for its pharmaceutical importance has been discussed in detailed account.

 

KEYWORDS: Drugs, device, in vitro, in vivo, inflammable, gases, pharmaceutical gases.

 

 


INTRODUCTION:

Gases have long been an established aid to the medical profession and year after year, researchers and technicians continue to discover new, successful applications. Gases assist with respiration and anaesthesia, allow specialists to study the functioning of the lungs and cardiovascular system, are essential tools in diagnosis and cryosurgery, and - when they meet the necessary specifications – can also be used to operate and calibrate medical measuring apparatus. Liquid nitrogen and helium have already proved their worth in the field of MRI imaging. In other words: Gases are an essential part of modern medicine. [1-3]

 

Medicinal gases are of various kinds depending upon their medicinal applications.

·      Gases for respiration

·      Gases used in anaesthesiology

·      Supplying coolants for MRI imaging

·      Gases for the clinical laboratory.

·      Surgery, medicinal baths, cryomedicine and gases for medical lasers.

·      Gases for diagnostics (e.g. for lung function tests, respiratory gas and blood gas analysis).

·      For general laboratory use: Gases in small containers and gas handling equipment.

 

GASES FOR RESPIRATION:

Oxygen and various gas mixtures are used when the body’s gas regime is disrupted. When the body is subjected to unusual stresses or respiration is weak as a result of inhaling anaesthetics or other substances that have a paralysing effect on the respiratory centre, the use of pure oxygen is indicated.

 

 


Table no: - 1.  No USP Specifications, but Manufactured using USP/NF Ingredients, not for Human Consumption.

Product

Applicable specifications

Used in vivo (drugs)

Used in vitro (device)

Prescription required by federal for administration

Air

USP

YES

YES

YES

Carbon dioxide

USP

YES

YES

YES

Helium

USP

YES

YES

YES

Nitrogen

NF

YES

YES

YES

Nitrous Oxide

USP

YES

YES

YES

Oxygen

USP

YES

YES

YES

Inhalation/Blood Therapeutic Gases

USP/NF

YES

YES

YES

Blood gas Calibration Mixture

FDA

NO

YES

-------

Xenon and Xenon Mixture

FDA

YES

YES

YES

Lung Diffusion Mixture

FDA

NO

YES

YES

Laser Mixture

FDA

NO

YES

-------

 


 

Figure No.1 Medicinal Gas Cylinders.

 

The Carbogen gas mixture (5% CO2, balance O2) is used to assist and stimulate respiratory activity. Carbogen (mixture OF carbon dioxide and oxygen) is just one example of the wide and varied range of gas mixtures that are available and can be supplied to support the respiratory function. Options range from simple mixtures such as “synthetic air” to complex mixtures that include stable isotopes. All gas mixtures are manufactured to very high standards of precision and reliability using state-of the-art technology, and the entire production chain is subject to a stringent quality assurance process.

 

● Oxygen for medical purposes:

Oxygen for medical purposes is supplied in specially prepared steel cylinders (from a separate cylinder store) with chromium-plated cylinder valves.

 

General characteristics:

A colorless, non-flammable, and odorless gas.

Health hazards:

None listed

Flammable limits:

A strong oxidizer.

Molecular weight: 32.00

 

Oxygen was known to be the only element that supports respiration as early as 1800 and was first used in the medical field in 1810. However, it took about 150 years for the gas to be used throughout medicine. In the early to mid 20th century oxygen therapy became rational and scientific, and today modern medicine could not be practiced without the support that oxygen supplies. [4-7] Medical oxygen is used to:

·      Provide a basis for virtually all modern anaesthetic techniques

·       restore tissue oxygen tension by improving oxygen availability in a wide range of conditions such as COPD, cyanosis, shock, severe hemorrhage, carbon monoxide poisoning, major trauma, cardiac/respiratory arrest

·      aid resuscitation

·       provide life support for artificially ventilated patients

·      Aid cardiovascular stability.

 

Figure No. 2.Containers: steel cylinders, for administration to patients


Table No.2. Specifications of Medicinal gas cylinders

Water Capacity  (Liters)

Exterior Diameter (mm)

Length (mm)

Total Weight (KG)

Filling Pressure (bar)

2

10

50

100

140

229

490

970

1640

6

17

79

200

200

200

 


Carbogen:

A carbogen mixture of 95% oxygen and 5% carbon dioxide can be used as part of the early treatment of central retinal artery occlusion. Its use in combination with nicotinamide is also being investigated in conjunction with radiation therapy in the treatment strategy of certain cancers. Because increased tumor oxygenation improves the cell-killing effects of radiation, it is thought that the inhalation of these agents during radiation therapy could increase its effectiveness. 3.Containers: steel cylinders, for administration to patients.

 

Table No.3. Specifications of Medicinal gas cylinders for patients administration.

Water capacity

 (litrs)

Exterior diameter

(mm)

Length

 (mm)

Total weight

 (kg)

Filling pressure

(bar)

10

50

140

229

970

1640

17

79

188

188

helium-oxygen mixture (20 % O2, balance He)

 

Heliox is a breathing gas composed of a mixture of helium (He) and oxygen (O2). Heliox is a medical treatment for patients with difficulty breathing. The mixture generates less resistance than atmospheric air when passing through the airways of the lungs, and thus requires less effort by a patient to breathe in and out of the lungs.

 

Table No.4.Containers: steel cylinders, for administration to patients

Water capacity

 (litrs)

Exterior diameter

 (mm)

Length

 (mm)

Total weight

 (kg)

Filling pressure

 (bar)

10

50

140

229

970

1640

17

79

200

200

 

● Compressed air:

Compressed air is also used during anesthesia as a substitute for nitrous oxide to reduce the high concentration of oxygen exposure. While the source of medical air may be a manifold with a bank of compressed air cylinders, most hospitals use a compressor system.

 

Table No. 5.Containers: steel cylinders, for administration to patients

Water capacity

(liters)

Exterior diameter

 (mm)

Length

(mm)

Total weight

 (kg)

Filling pressure

 (bar)

10

50

140

229

970

1640

17

79

200

200

 

● Other Respiratory gas Mixtures:

These are produced to order, according to the requirements of the specific application. For example, the mixture of respiratory gases used by divers operating at great depths must be adjusted with care. In this case, the nitrogen is partially or completely replaced by helium.

 

GASES USED IN ANAESTHETICS:

The purpose of anaesthetic agents is to induce a condition in the patient whereby sensations of pain and consequently muscle contractions, and hence also defensive reactions, are massively attenuated or even neutralised altogether. If the patient also loses consciousness, this is termed general anaesthesia or narcosis.

 

● Nitrous Oxide:

Nitrous oxide is the most commonly used inhalation anesthetic in dentistry, When used alone, it is incapable of producing general anesthesia reliably, but it may be combined with other inhalation and/or intravenous agents in deep sedative/general anesthestic techniques. The inhalation agents are most deserving of the title, general anesthetics. These are excellent hypnotics, and at higher concentrations, they provide varying degrees of analgesia and skeletal muscle relaxation. Although the mechanism for their anesthetic effect is unresolved, influences are directly related to their tension (partial pressure) in brain tissue. This follows an equilibration between tensions in the inspired gas, the alveoli, and arterial blood.

 

Liquefied Compressed General characteristics:

A colorless, nonflammable, odorless, sweet tasting, anesthetic, liquefied gas.

Health hazards:

A simple asphyxiant and an anesthetic, a mild oxidizer.

Flammable limits:

Nonflammable

Molecular weight:

 44.00

 

● Xenon:

This rare gas (Xe) both produces a more powerful anaesthetic effect and is more fat-soluble than nitrous oxide. Using modern closed-circuit anaesthetic apparatus, this expensive gas can be reclaimed and put back into circulation again. Xenon is currently undergoing clinical trials as an inhalable anaesthetic.

 

Liquid Helium for MRI Imaging:

Liquid helium is used to cool down the superconductive magnets coil in MRI scanners to a temperature below 10 Kelvin. Superconductivity is a physical effect that occurs in various materials when they are subjected to extremely low temperatures. Unlike other imaging procedures used for diagnosis, MRI allows high-contrast images of soft tissue to be generated without the use of high-energy ionising rays. The primary tools used to generate the external stationary magnetic field are superconducting magnets. These are capable of generating very powerful homogeneous magnetic fields, a prerequisite for high-contrast images. Superconductivity “is the complete disappearance of electrical resistance in a substance. This phenomenon only occurs below the transition temperature specific to each material. Niobium-titanium alloy, which is used for the coil of a superconducting magnet, has a transition temperature of -263.7 °C. The only cryogenic gas capable of generating such extremely low temperatures is liquid helium. The coil is immersed in a liquid helium bath at a temperature of -268.9 °C (4.22K), whereby a certain amount of liquid helium evaporates and has to be replaced.

 

Gases for the Clinical Laboratory:

Gases and gas mixtures are not just required for diagnosis and anaesthesia. They also provide essential assistance to clinical researchers and research laboratories.

 

● Carrier gases:

These are used, for example, to transport the sample being analyzed through the separation column of a gas chromatograph into the downstream detector system.

 

● Zero gases:

 These contain the calibration component to be measured in a concentration that is below the level of detection of the measuring systems being employed. They are used to set the zero point in gas analyzers, and as a gas that is free of the component to be measured, for purging.

 

Surgery, Medicinal Baths:

Carbon dioxide in surgery and medicinal baths minimally invasive surgery is an integral part of modern medicine. And insufflations with carbon dioxide makes endoscopic procedures substantially easier to perform. In baths, carbon dioxide creates a sensation of warmth and acts as a vasodilator for the skin by stimulating its heat receptors.

 

● Carbon dioxide:

For medical purposes carbon dioxide for medical purposes is supplied in specially prepared steel cylinders (from a separate cylinder stock) with chromium-plated cylinder valves.

 

Figure No. 3. Cylinder stock (steel cylinders with chromium-plated cylinder valves.

 

Table No.6.Containers: steel cylinders, for administration to patients

Water capacity

 (litrs)

Exterior diameter

 (mm)

Length

 (mm)

Total weight

 (kg)

Filling pressure

 (bar)

2

8

100

140

490

805

6.8

16.5

57.29

57.29

 

Cryomedicine:

Thanks to progress in low-temperature techniques, Cryomedicine has become an established medical technique. This technique exploits the effects of exposing cells and tissue to cryogenic liquid nitrogen at the extremely low temperature of -196 °C. Application of very low temperatures performs two important tasks:

·      Cryoconservation e.g. of cells and tissues

·      Cryosurgery e.g. deliberate destruction of unhealthy tissue Other applications are in Cryotherapy. Here, a cold gas mixture produced from cryogenic liquid nitrogen is used as atherapeutic aid.

 

Gases for medical lasers:

Various gas mixtures are used for medical lasers. CO2 and Excimer lasers have emerged as new surgical tools in modern medicine.

 

Figure No. 4. Setup of Medical Laser

 

Calibration gas mixtures:

Calibration gas mixtures are high-precision gas mixtures used to calibrate measuring equipment. They also play an important role in various processes and in experimental research, whenever mixtures with precisely defined and precisely measured compositions are required. Calibration gas mixtures are used in medicine primarily for:

·      Calibration of measuring apparatus in laboratories; for example, to calibrate gas analyzers that run on various physical or physico-chemical principles.

·      Creation of precisely defined atmospheres in order to test gas alarm systems.

 

Gas mixtures consisting of oxygen, helium, xenon or nitrogen as the balance gas, plus carbon dioxide, carbon monoxide, stable carbon monoxide isotope (C18O), nitrogen monoxide, oxygen, helium, argon, xenon or sulphur hexa- fluoride as the calibration component.[7-10]

 

Typical Applications:

Blood gas/ respiratory gas analysis:

High-precision gas mixtures are used to monitor the acid/base and blood gas status (pH value, partial pressure of O2 and CO2) and to measure the composition of inhaled and exhaled air. One of two methods is commonly used to take these measurements:

·      Equilibration, that is, saturation of the blood sample with CO2 gas mixtures, followed by a measurement.

·      Direct measurement of the sample in question.

 

Table no.7.Example for Standardize Gas Mixture

CO2

O2

N2

SYNTHETIC AIR 20% O2 BALANCE N2

2%

5%

5%

6%

4%

5%

10%

15%

2%

12%

20%

12%

BALANCE

BALANCE

BALANCE

BALANCE

BALANCE

 

BALANCE

BALANCE

 

 

 

BALANCE

 

● Gases for lung function tests:

Lung functions tests are primarily used to measure static lung function values (functional capacity, ability to work) both in healthy individuals and in cases of respiratory infection or disease. Lung functions tests are primarily used to measure static lung function values (functional capacity, ability to work) both in healthy individuals and in cases of respiratory infection or disease. Gas mixtures are used in spirometry, usually with a proportion of some rare gas such as helium which the body cannot easily resorb. In order to measure static lung function values, e.g. diffusion capacity using the single-breath method, gas mixtures containing CO and He are predominantly used. Other available standard mixtures O2/He, O2/He/N2 mixtures.

 

For General Laboratory Use Gases in small containers:

 For many applications, large gas cylinders are too cumbersome to handle. Other circumstances, such as low or merely sporadic gas requirement, safety considerations, technical requirements and so on, may also call for more convenient forms of gas supply.

 

Gas Handling Equipment:

When pure gases, precision calibration gas mixtures and other gas mixtures are transferred, it is much more important that their purity and composition be maintained when the gas is withdrawn from the cylinders and distributed to the actual point of use than in the case of industrial gases.

 

Regulating Valves:

These are used to withdraw gases without pressure control. They can be set to maintain a given gas flow rate. In closed systems, they can be used to maintain a pressure up to the level of the cylinder pressure.

 

Pressure Regulators:

These are used to reduce the pressure of compressed gas from high pressure down to a constant, lower withdrawal pressure. [10-13]

 

CONCLUSION:

There are many gas mixtures used for clinical and medical applications. They are often used for patient diagnostics such as lung function testing or blood gas analysis. Test gases are also used to calibrate and maintain medical devices used for the delivery of anaesthetic gases. Gases such as oxygen, nitrous oxide, nitrogen/surgical air, carbon dioxide, oxygen/nitrous oxide, medical vacuum, anaesthetic gas scavenge/waste anesthetic gas disposal and medical air to various parts of the facility. Source equipment systems are monitored by central/source alarm systems, at the point of supply with multiplexed repeater alarms throughout the facility and for monitoring high and low gas pressure in particular areas such as general ward, operating theatres, ICU/ITU/CCU/NICU, recovery, major treatment rooms, etc.

 

REFERENCE:

1.     A.H. Beckett and J.B. Stenlake, Practical Pharmaceutical Chemistry, Part-I. The Athtone Press, University of London, London.

2.     P. Gundu Rao, Inorganic Pharmaceutical Chemistry; Vallabh  Prakashan, Delhi.

3.     Advanced Inorganic Chemistry by Satya Prakash,  G.D. Tuli Jolly-Modern Inorganic Chemistry Pharmaceutical Inorganic Chemistry textbook by Alagarsamy L.M. Atherden, Bentley and Driver’s Textbook of Pharmaceutical Chemistry Oxford University Press,  London.

4.     Indian Pharmacopoeia 1996, 2006.

5.     J.H Block, E. Roche, T.O Soine and C.O. Wilson, Inorganic Medical and Pharmaceutical Chemistry Lea and Febiger Philadelphia PA.

6.     Pharmaceutical Inorganic Chemistry by S. Chand, R.D. Madan, Anita Madan

7.     Pharmaceutical Inorganic Chemistry by Soma Shekar Rao

11.   http://www.globalspec.com/

12.   http://www.rsc.org/Learn-Chemistry

13.   https://medicalgasresearch.biomedcentral.com/

 

 

 

Received on 08.12.2016       Accepted on 22.01.2017     

© Asian Pharma Press All Right Reserved

Asian J. Res. Pharm. Sci. 2017; 7(1): 08-12.

DOI: 10.5958/2231-5659.2017.00002.9