Abstract

In several pharmacologic, pharmacology, and alternative medicine studies, oral administration of medication or test substances to experimental animals is needed. It is clinically sound and recommended to administer test substances to experimental animals along the same route that they are taken or expected to be taken by humans as general bioavailability; the pharmacology and pharmacology parameters obtained for the drug will depend significantly on the route chosen to administer it. The lack of ready access to high-quality oral tubing built for different species, as well as a widespread lack of technical expertise to properly use out-of-the-box techniques in this part of the world, has made this route controversial among medicine scientists. The typical problems and difficulties associated with the oral administration of test product solutions were avoided by mistreating either the syringe alone or incorporating it into the animals' feeds or drinkables. This jury-rigged oral tubing was also used to ensure that the expected doses were correctly administered in each case.

Key Words

Oral Administration, Experimental Animal, Cannula

Introduction

The most popular form of medication administration to humans is oral administration. It's also the fastest, most comfortable, and most cost-effective alternative. Where oral therapy is not necessary because the patient is noncompliant, unconscious, or unable to absorb what is offered by mouth, parenteral therapy is used. The injection of a drug to laboratory animals necessitates careful consideration, with the goal of maximizing the agent's distribution while minimizing the animal's potential for adverse reactions. The instrumentation that is used to distribute substances to animals is determined by the duration of the study as well as the type of fabric that is being applied. Additionally, Upon the administration of the suspensions or solutions, Methods of vehicle incorporation and vehicle itself must be chosen carefully. The testing team, veterinarians, and technical staff should keep in mind the reasons for choosing a package for drug distribution and carefully consider how substances would be prepared and stored before being administered to animals. Failure to consider these factors during the design of experiments could result in unintended negative effects on experimental animals and muddled results.

In toxicology, pharmacology, medical specialties, and drug development trials, oral administration of materials may be a standard practice. Oral delivery is less invasive than other widely used body routes, such as blood vessel and intraperitoneal administration, and may be a more physiological and clinically applicable option for evaluating the effectiveness of medication for treating human diseases, since most human medication is taken orally. The intra-gastric feeding procedure, which includes handling and restraining the animal, inserting a feeding needle into the esophagus, and injecting the drug directly into the abdomen through a syringe, is often used to achieve oral administration in conscious animals. Oral feeding, despite its efficacy, has been linked to metastasis involvement, abdominal distension, and the production of granulation inside the cavity after repeated dosing. Furthermore, as seen in a recent study, the strenuous restraint of warning animals necessary to escape technical complications triggers stress responses that have a major effect on physiology and alter experimental outcomes. These intra-gastric feeding problems can be more difficult if the handler is inexperienced or inept in animal handling.




Oral Dosing

Instruments used for stomachic forced feeding, pilling (including capsule administration), and powdery diet are the most widely used for oral dosing. Water bottles affixed to the caging are used to administer liquid and soluble substances directly or as binary compound solutions for voluntary use.




Gavage

To avoid the intra-tracheal dosing and any aspiration chances and to prefer the unconditioned reflex, animals are given the oral dose in their state of consciousness. For this purpose, we can use the feeding needles that are curved or may be straight and also the medication gavage tubes. Advantage of the ball tipped needles that are stainless is that they are easy to sterilize and clean, but the disadvantage is that it imposes a greater risk of rupturing the muscle system if it is pushed into the body. Tissue injury risk or the puncture can be minimized by using the plastic or rubber feeding needles having narrower and more adaptable rubber, but it requires the mouth gag to be used in larger animals because they may chew the needles if not properly placed inside their mouth. For the acute or more frequent but fixed doses can be accurately given using the nasogastric tubes for several days to hold a suture. We will require a Elizabethan collar incase if nasogastric tubes is placed on the left side so that the animal can be prevented from dislodging the tube. Whereas some animals do not enable us to use to these collars. Moreover, permanent inborn reflex can occur in cases of the chronic tube replacements.




Pilling or Bolus Delivery

Pills and capsules are issued to rodents weighing more than 150 grams for example cats and dogs as well as rabbits using balling arms. Pill and the plunger can be hold together by using the slender, onerous and long metal or plastic tubes having a small slot at its top and it can be done accurately until the administration of the pill at the back of the animal's tongue. Hence the capsules can be administered to the abdomen or the distal passageway of the rodents. Pill can also be inserted using an alternative method into the hollow conduit tip and making it a gastric tube through the stomach. After the tube is at its postion we can force the air bolus into the conduit to dislodge the pill. We can use the lubricant that is oil based in order to avoid the compromise the integrity of the capsule in case they are made of gelatin because the water content will dissolve it. As the tube of the lumen is at risk of blocking by the pill, so proper tube can be positioned and ensured only after the pill is dispensed.




Medicated Food and Food Treats

Commercially available pre-formulated treats containing a variety of medications are available for a variety of animals, and personalized treats may also be made. Pelletized diets are often purchased or modified to include drugs or substitute ingredients in precise doses. Electronically regulated feeders that can automatically operate themselves because times are preset for opening and closing, are available in specialized cages to hold or restrict the number of medicated diets eaten, as well as to monitor the temporal order and length of feeding sessions. For dogs and larger animals, similar gating devices with a radiofrequency-emitting collar are helpful to monitor or document access to prescribed medication feeds.

Laboratory Animals

Worldwide Guiding Principles: A Tool for Harmonization

Globalization of science and moral qualities have prompted usage of guidelines on security of creatures utilized

for logical purposes around the world, in view of the standards of substitution and refinement. In any case, while guidelines in individual nations are by and large dependent on these standards, there are varieties in the way they are essentially applied. Consequently, worldwide, and worldwide associations have created core values to fit creature care and utilize and have given suggestions, which can be comparatively applied regardless of the administrative structure working in a specific country.

 

Oversight of Research Animal Welfare in the United States

The utilization of creatures in exploration in the United States (US) is represented by various longstanding guidelines and guidelines. The Animal Welfare Act and Regulations declared by the US Department of Agriculture, Animal Plant Health Inspection Service, administers explicitly characterized vertebrate creatures utilized for research, testing, educating, presentation, and trade. This government law gives explicit necessities to creature care, which incorporates angles from support and institutional survey to veterinary consideration and revealing. The Guide gives a nitty gritty arrangement of execution guidelines incorporating significant subjects like Institutional Animal Care and Use Committee (IACUC) design and capacity, word related wellbeing and security, creature climate and the board, veterinary consideration, and actual plant. The cornerstones of the US regulations and guidelines are the IACUC, the Institutional Official, and the central role of the attending veterinarian. All must work together in providing an animal care and use program that ensures the well-being of animals and the integrity of science.

 

Mice

The mouse and human genomes are about 85% the equivalent, and the similitudes have made the mouse a ground-breaking model for examining human science and sicknesses. Dealing with, blood assortment, and medication organization are same as rodent.

 

Table 1. Details of the Mice

Lifespan	1-3 years
Adult weight	M 20-30g, F 18-35g
Birth weight	1-2g
Heart rate	310-840 beats/minute
Respiratory rate	80-230 breaths/minute
Body temp.	36.5-38 C

 

Rats

Rats were first utilized for exploratory purposes during the 1800s, deliberately reared rats are utilized in creature testing for various reasons, including their successive multiplication, hereditary virtue, and similitudes to human science.

 

Table 2. Details of the Rats

Lifespan	2.5-3.5 years
Adult weight	M 300-500g, F 250-300g
Birth weight	5-6g
Heart rate	330-480 beats/minute
Respiratory rate	85 breaths/minute
Body temperature	35.9-37.5°C

 

Frog or Toad

physiological Studies

Guinea pig: hypersensitive test (allergic reaction) or the screening of anti-asthmatic drugs

 

Rabbit

expensive, the effect of some drugs

Solid or Liquid Dosage Forms or Substances to be Administered Via Oral Route

Introduction

Prior to controlling any substance (remedial or test) to a creature subject, one should think about the pH, sterility, and synthetic nature (scent, taste, mucosal touchiness, osmolarity, dissolvability, light affectability, and risk status) of the compound and settle on proper choices on the portion to be managed, recurrence of organization, volume to be directed, the dissolvable (if important), and course of organization.

 

Parameters

Name of compound or a concise synthetic portrayal if not by and large known (except if restrictive).

Ø  Dose (mg/kg) of compound.

Ø  Route of organization

Ø  Volume of organization.

Frequency of organization, and spans between rehashed organization Information on dissolvable/vehicle including pH and other substance attributes.

Effects of compound as well as vehicle including planned impacts and results.

 

Characteristics of Compound and Solvent (Vehicle)

pH

Know the pH of the compound AND the vehicle. Focus on pH ~7. On the off chance that the pH is sequential attempt one of the accompanying:

 

Cushion to pH 7 if conceivable

Weaken the arrangement utilizing clean typical saline or PBS

 

Sterility

Filtration and other cleansing methods are required to deliver the compounds maintaining their sterility. Only those compounds are allowed to be regulated that are mixtures of pharmaceutical grades.

 

Odor

Voluntary intake of the compound is sometimes affected by the odor of the compound that can be offensive.

 

Taste

Some mixtures that are prepared in the normal water must be having sucrose in order to improve their taste that can be very bitter otherwise and effect the intake. These incorporate yet are not restricted to antibiotic medication, doxycycline, and metronidazole. 2.5 to 5 grams of the sucrose can provide a satisfactory improvement in the taste of the solution.

 

Mucosal Peevishness

PI to check tissue similarity while applying to the mucosal surfaces while directing such mixtures, for example to the windpipe or to the eyes.

 

Osmolarity

Osmolarity should be 280 osmoles i.e. iso osmolar in case of the parenterally administered mixtures.  For example, the Lactated ringer solution containing dextrose 5% is itself iso osmolar without help from anyone else, delivers the water and CO2 causing the resultant mixture to be iso osmotic as well. Be that as it may, alert is exhorted in a got dried out creature.

 

Solubility

Some substances are insoluble in water requiring them to be incorporated into a suspension form. A model is

sulfamethoxazole trimethoprim suspension that is controlled in the normal water.  Regular shaking is required in this suspension to get the accurate dose on daily basis.

 

Light Affectability

By using a glass cover foil made up of plastic or rubber or even by using the glass that is hued. Some antibiotics like the sulfa and trim are incorporated in this way.

 

Toxicity

PI to report any substance or a vehicle that is new to be directed to creatures to decide limits to utilize and results.

 

Oral Dose Equipment

Powdered diet, gastric gavage and sometimes pilling are the most commonly used equipments for the oral dosing even including the capsule administration.

Liquid and water-dissolvable stuffs usually can be administered either by incorporating into an aqeous solution for the voluntary feeding by the animals by placing them in their cages or administered directly.

 

Table 3. Types of Needles and Gavages that are used for Oral Administration in Animal

Stretchy or Firmly Straight Needles	Ball-Tipped Stainless Steel Needles	Nasogastric Tubes
Stretchy or firm straight or arched gavage needles as well as nasogastric pediatric  feeding tubes have less possibility of tissue rupture.	Ball-tipped  stainless  steel  needles can be easily clean  and sanitize though have a great esophageal breach risk,   if  their  passage  is  enforced into the animal's mouth.	They may be  used for critical dosing in large animals or may be affixed in place for some days via stay suture  or by using surgical glue drop.
but if they are not located properly in animal's mouth then they may be crushed by animal.		An Elizabethan collar may be required  to  avert  animal  from  removing  tube.
and to use for animals with large size then they require a mouth gag.		Few animals don't gladly bear these collars.
		Chronic tube placement might cause frequent emesis in few animals.

 

Procedure for Oral Administration in Animals

Materials Required

Ø  Feeding needles or metal gavage of appropriate size

Ø  Feeding needles or plastic gavage of appropriate size

Ø  Red Rubber Flexible Feeding Tube - 8fr (for Rats only)

Ø  Syringes of suitable size

Ø  Administrating Solution or complex mixture

Ø  Towel (if required) to wrap rats if flexible red rubber feeding tubes are used

 

Table 4. Suggested Maximum Administration Volume and Gavage Needle Size

SPECIES	GAUGE	LENGTH	BALL DIAMETER	VOLUME	EXAMPLE
MOUSE	24-20 G	2.5-3.8 cm	1.25-2.25 mm	<10 ml/kg	For a mouse of 25gm, 0.25ml would be maximum volume
RAT	20-16 G	3.8 – 10 cm (1.5-4”)	2.25-4.0 mm	<10 ml/kg	For a rat of 250 gm, 2.5 ml would be maximum volume

Figure 1

Metal gavage, plastic gavage needles and red rubber feeding tubes for rats



Procedure

To calculate maximum volume to be administered, first of all weigh the selected animal

Then select gavage needle finest for your use. For mice and rats, there are flexible plastic and metal feeding needles in numerous dimensions. 

Metal gavage needles are usually easy to use for mice as they can’t morsel the tube but are at higher risk to harm esophagus if mouse scuffles.  

Curved or straight metal gavage needles are accessible but their choice hinge on individual penchant and practice.  

Flexible plastic gavage needles (for rats or mice) or red rubber feeding tubes (for rats) are less likely to damage esophagus. Though animals can morsel them and they also need some training to use efficiently.

Measure distance from the oral cavity to the end of xiphoid process that is the sternum’s caudal point, by using feeding tube or needle on restrained animal’s outside, before performing oral gavage procedure. This would be the expanse for needle to be introduced into esophagus. By using a small piece of tape or a permanent marker, mark this distance on needle.

Measurement of distance from oral cavity to xiphoid process in Ra


With accurate volume of compound to be administered, pre-fill the syringe and gavage needle or tube. In order to ensure accurate dosing and to avert the animal from tasting possibly bitter mixtures, wipe the outside of needle or tube to remove any of mixture that may be coating the outside of needle or tube.


Restraint
MICE: Softly take out the animal from cage and inflexibly restrain animal in an upright position. Catch a good scruff of skin over the mouse’s shoulders, in this way front legs are stretched out to side and neck and head are restrained. Make sure that animal can breathe freely by watching if the chest is moving.
RATS: Softly take out the animal from cage. For using a plastic or metal gavage needle, detain rat in an upright position by using either a crossover or v-hold to restrain the head and neck. Make sure that animal can breathe easily. For using a red rubber flexible feeding tube, rat can be smoothly controlled or by wrapping in a towel by hand however they are sitting flat on a counter or table.


Gavage Procedure
Plastic or Metal Gavage Needle: Glide gavage needle’s end into left side of mouth of animals in front of first molar and behind front teeth, along with the  roof of animal’s mouth slowly to animal’s left side. Animal usually “gags” at this stage, when gavage needle is at the end of mouth. With mild pressure from gavage needle, slightly lean the head back towards spine. This will let esophagus to be in a straight line with stomach. When passing the gavage needle, there should be no resistance and gavage needle should glide down the esophagus with gravity alone.  Gavage needle might requisite to be a little perverted clockwise as it passes the epiglottis then into esophagus. Till pre-marked line touches the mouth, keep passing needle into esophagus. 
Red Rubber Feeding Tube (for rats only): In order to prevent front feet of rat to grab hold of feeding tube, hold rat on a counter or table or cover the rat lightly in a towel.  The feeding tube is glide down into left side of the rat’s mouth, above the tongue to back of the throat, in a straight line with the stomach. Until pre-marked line touches the mouth, keep passing the needle into esophagus. Gently restrain front limbs of rat as rat may habitually try to twitch tube by its front paws.
Make sure that animal is breathing easily when feeding tube or needle is at pre-measured distance. And inject a small test dose of approximately 0.05 ml. Gradually introduce the solution for 2 to 3 seconds to reduce liquid approaching back up the esophagus, if having no change in breathing exertion. To inject viscous or oily ingredient, then smallest possible volume should be used, and introduce more gradually that is over 5 to 10 seconds, then take out needle slightly, thus none of the matter is brought back up the esophagus into back of the throat. Gulping any oily matter into lungs may lead to death of animal.

Note: Instantly remove gavage needle from esophagus and relieve the restraint, if the animal is not breathing properl
Take out the feeding needle gently, in opposite direction from insertion when the entire substance has been administered then return animal to its cage.
In order to observe for possible problems, observe the animal for at least ten minutes. If there were any problems like extreme struggling or evident aspiration, observe the animal until it is behaving naturally before leaving the animal for the day.

Conclusion

A central important aspect of many research projects and clinical trials is the administration of substances to animals via various routes for example oral route. To ensure that experiments involving the experimental administration of substances to animals are adequately prepared and performed, several considerations must be addressed by the study staff, veterinarians, institutional animal caregivers, and members of the animal ethics committee involving dosing of the drug regarding the weight of the animal and the route specified in the administration that shows maximum safety and efficacy and also handling of the animal during the administration to ensure voluntary and safe administration of therapeutic agents to the animal. Experimental refinement and minimization of adverse effects on animals regarding administration can be improved by close attention to detail of the medicine on the label and consideration of the route of administration for successful and accurate experimentation to ensure a minimum margin of error in the result obtained

References

• Abe, C., Tashiro, T., Tanakam K., Ogiharam R., Morita, H. J. (2009). a unique style of implantable and programmable infusion pump for tiny laboratory animals. J Pharmacol Toxicol strategies 59:7-12
• Abell, P., Pangilinan, G. N., Chellman, G. J. (1995). Novel restraint device for oral dosing of rabbits. Contemp high research lab Anim Sci 34:86-87 African Journal of Biotechnology Vol. 8(6), pp. 960-964, 20 March, 2009
• African Journal of Biotechnology Vol. 8 (6), pp. 960- 964, 20 March, 2009