Vol 3, Issue 1, 2021 (26-37)

http://journal.unpad.ac.id/idjp

*Corresponding author,

e-mail: y.herdiana@unpad.ac.id (Y. Herdiana)

https://doi.org/10.24198/idjp.v3i1.33632

Veterinary Drug Development from Indonesian Herbal Origin: Challenges and Opportunities

Yedi Herdiana

, Nasrul Wathoni

, Sriwidodo

, I Ketut Mudite Adnyane

Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas

Padjadjaran, Sumedang 45363, Indonesia.

Departement of Anatomy, Physiology, and Pharmacology, Faculty of Veterinary Medicine, Bogor

Agricultural University (IPB University), Indonesia.

Received: 3 March 2021, Revised: 22 March 2021, Accepted: 27 March 2021, Published: 1 April

2021

ABSTRACT

Herbal medicine is increasingly being used in human and veterinary medicine to reduce

and prevent minor ailments and support conventional treatment using allopathic

medicine. The medicinal properties of the plants used in phytotherapy are due to the large

number of active compounds found in the plant kingdom. The active compounds

extracted from the plant is often equivalent to a synthetic drug according to its therapeutic

efficacy; thus, they are used in veterinary medicine, primarily as antibacterial,

antimycotic, antiparasitic, disinfect, and immunostimulant.pharmaceutical quality,

ensuring safety, specific standards of purity, and consistency. These standards apply

throughout the production and formulation process. This review describes the

development of herbs that can be used as veterinary drugs with the possibility of dosage

form technology. Veterinary dosage forms show great promise for the future of the herbal

veterinary delivery system.

Keyword: Veterinary drug, herbal medicine, dosage form, drug delivery.

1. Introduction

Veterinary medicine is the branch of science

that applies medical, surgical, public health,

dental, diagnostic, and therapeutic principles to

nonhuman animals. Animals provide us with

companionship (e.g., Dog and cat), recreation

(e., g. Horse), food (e.g., Cattle and pig), and

manual labor (whether an elephant carrying

logs in Thailand or a hunting dog retrieving a

downed pheasant in South Dakota). Just like

humans, these animals have received medicines

to keep them healthy, and the reasons for

producing single-dose veterinary dosage forms

are the same as those in humans; to permit

delivery of action in a form that is effective,

safe, and able to be handled and administered

by the end-user 1–3.

Animal care and animal welfare in rural

populations is based on ethnomedical

veterinary practice, especially when access to

western veterinary products is difficult or too

expensive. The cost of using veterinary drugs

accounts for more than 50% of all medical

expenses. Synthetic veterinary drugs have

adverse side effects, such as drug resistance and

increased toxicity in animals due to excessive

doses 4. Side effects of synthetic drugs, such as

Y. Herdiana et al / Indo J Pharm 3 (2021) 26-37

antibiotic residues, cause antibiotic resistance

in humans; toxic metabolites remain in the meat

5. Synthetic drug side products are a concern in

the long-term use of these drugs. Problems like

this have prompted the search for alternatives

such as herbal medicines, as they are cheap and

safe compared to modern animal health care

systems 6.

Medicinal herbs contain various

pharmacologically active ingredients, and each

herb has unique combinations and properties 6.

Veterinary herbal medicine can be applied for

therapeutic, prophylactic, or diagnostic in

animal health care. The use of herbal medicines

is considered to have no side effects or minimal

side effects, non-narcotic product, available

quickly and at an affordable price. Traditional

veterinary knowledge consists of a collection of

beliefs and practices about animal welfare that

involve the use of natural resources [4]. The

demand for plant-based drugs is increasing in

both human and veterinary medicine [7-9].

Alternative medicine is becoming popular all

over the world, and herbal medicine has

become one of the most common forms of

alternative therapy and complementary therapy

and supplements to allopathic medicine [8].

Indonesia is a country that has a wealth of

herbs. In ethnopharmacology, many plants are

commonly used as medicine in animals 7.

There are great opportunities for herbal

development for veterinary, as regulated by

Kepmentan No 453/2000 concerning Natural

Medicines for Animals. Animal treatment

using herbal medicines, according to the

government, must be standardized through

research. After passing scientific research and

testing, herbal medicines must obtain approval

from the Ministry of Agriculture or be

registered 8. Livestock disease is one of the

biggest obstacles in improving the quality of

livestock production. Farmers need the best

medicine to treat diseases that attack livestock

[10].

Like human medicine, pharmacists are

expected to design, manufacture and control

veterinary drug delivery systems. On the other

hand, some drugs or drug formulations may not

be suitable for animals. The design and

preparation of veterinary drug delivery systems

requires consideration and challenges

compared to preparations for humans. 3,9,10.

This review provides an overview of the use of

herbal medicine in veterinary studies from

various studies. Special considerations and

developments are needed to change the

empirically used preparations into drug

delivery systems that are easier to use, stable,

and have more benefits. This review provides

an overview of the great potential of Indonesian

herbs and how to empower them to be more

scientific and effective as a herbal medicine

veterinary.

2. Plant Used in Herbal Veterinary

Herbal drugs usually used in human practice

are often utilized in pets, particularly by owners

who used such remedies for themselves (6).

They are given to companion animals to treat

respiratory, skin, urinary, digestive, and

cardiovascular affections and to reduce stress;

moreover, they are also used to treat some

chronic diseases instead of conventional drugs

to avoid adverse effects that sometimes could

occur as a consequence of a prolonged

administration of synthetic drugs. Finally,

phytotherapy could represent valuable support

to conventional therapies in the case of severe

illness. While few studies have been carried out

to evaluate the therapeutic efficacy of herbal

remedies in companion animals, many studies

have been found in the literature relating to the

use of plants and plant materials in farm

animals (2).

Y. Herdiana et al / Indo J Pharm 3 (2021) 26-37

3. Dosage forms of veterinary herbal

medicines herbal medicinal products

Development of the principle of veterinary

medicine

The general property of a veterinary drug is that

it is not easy to predict the emergence of a

beneficial response when the body interacts

with veterinary drugs. The continued impact of

this trait will ultimately have implications such

as (i) generating favorable responses such as

Table. 1 Plant Used in Herbal Veterinary

Scientific name

Used parts

Use

Species

Reference

Cymbopogon

citratus

Leaves

Anthelmintic

Chicken

poultry

Zingiber

officinale

Rhizome/root

Antibacterial

Chicken

poultry

Rhizome/root

Phytobiotics

Chicken

poultry

Rhizome/root

Wound healing

Mice

Alpinia galanga

Rhizome/root

Antibacterial

Chicken

poultry

Rhizome/root

Phytobiotics

Chicken

poultry

Rhizome/root

Antifungal

Dog

Andrographis

paniculata

Leaves

Antibacterial, Imonomodulator

chicken

poultry

Leaves

Antibacterial

Cow

2122

Leaves

Hepatoprotector

Mice

Tamarindus

indica

Fruit

Weight gain

Chicken

poultry

Curcuma

xantorriza

Rhizome/root

Lactasion

Cow

25–27

Hepatoprotector

Chiken Poultry

Anthelmintic, Weight gain

Sheep

Kaempferia

galanga

Rhizome/root

Weight gain

Cow

Piper

retrofractum

Fruit

Aphrodisiac

Mice

Orthosiphon

aristatus

Herbs

Diuretic

Cattle

Allium sativum

Bulbs

Weight gain

Chicken

Poultry

Bulbs

Antibacterial

Cow

Carica papaya

Fruit seeds

Anthelmintic

Chicken

poultry

Hibiscus

sabdariffa

Leaves

Immunostimulant

Mice

Catharanthus

roseus

Leaves

Wound healing

Mice

expectations, (ii) the emergence of new

diseases in infected animals due to veterinary

drug administration. Other impacts are (iii)

causing residual hazards in processed products

of animal origin, (iv) causing contamination of

the habitat of infected animals. If the effect is

in the form of a beneficial response according

to the plan, it will not be a problem. However,

if the response is in the form of a new disease

caused by drugs, and/or it causes residues of

veterinary drugs and contaminants of animal

habitat. The problem will not benefit human

life. As a way out of the issues mentioned

above, it is time to change the orientation of the

management strategy towards a logical and

responsible direction [38].

The development of the cito principle has the

meaning as soon as possible to bring the drug

closer to the target pathological part of the

body. However, when the pathological part of

the body has recovered, then as soon as

possible, the drugs or medical equipment used

must be eliminated. The development of the

tuto principle has four meanings, namely (i)

safe when used as a means of treatment, (ii)

safe from the impact of contamination residues

on processed animal products, (iii) safe from

causing damage to animal habitat, (iv) safe

from abuse of animal drugs and veterinary drug

abuse. The development of the curare principle

has requirements, namely the selection based

on the patient's treatment strategy by designing

the dose, selecting the type of active ingredient,

adjusting the time and method of

administration, and determining the dosage

form. The development of the jucunde principle

has the meaning of having to accommodate

animal welfare criteria, including veterinary

drug preparations that must not cause

pain/hunger, (ii) fear, (iii) unpleasant taste for

animals. Another aspect of the jucunde

principle is that the activity of administering

veterinary drugs must create a sense of security

from possible attacks by animal sufferers to

make the drug giver comfortable 38

3.2 Dosage forms of veterinary herbal

medicines herbal medicinal products

Veterinary drug delivery is still rare in research.

From a total of more than 8000 research papers

focusing on delivering medical, veterinary, and

agricultural active ingredients published

between 1990 and 2020, only 3% are focused

on veterinary applications, 4% on agricultural

applications, and the rest of 93% on medical

applications [39].

Considerations in making dosage forms in

animals, have some of the same pharmaceutical

principles. Pharmaceutics is an

interdisciplinary science that involves the

integration of physical pharmacy,

pharmaceutical formulation, manufacturing

technology, dispensing pharmacy, and the laws

of pharmaceutics [40]. The same factors

influence the process of dosage form

development and quality control considerations

[41–43]. These factors include:

1. The physical and chemical characteristics

of the active pharmaceutical ingredient

(API) such as:

a. intrinsic solubility (aqueous solubility

of the unionized form of the drug);

b. pKa;

c. ability to traverse the biological

membrane;

d. stability:

e. in the presence of excipients

f. during manufacture

g. shelf life

h. crystal characteristics (e.g., crystalline

habit, particle size, particle shape).

2. The intended use of the dosage form:

a. targeted duration of drug release;

b. stability in the gastrointestinal (GI) tract

(orally administered products);

c. ease of administration;

d. limitations on dosage form:

e. size of tablets or capsules or volume of

an oral liquid

f. injection volume

g. location of administration (e.g., skin,

ophthalmic, ear).

3. Formulation that includes excipients to

insure that the product delivers the drug in

a manner defined by the

pharmacologist/clinical expert.

4. Method of manufacture (based upon drug

and intended dosage form characteristics).

Pharmaceutic principles are discussed from the

perspective of the design of drug delivery

systems (dosage forms), the formulation and

manufacturing variables influencing in vivo

and in vitro product performance, and the

product understanding necessary to assure that

the dosage form is effective, safe, and stable

[41–43].

From an evolutionary perspective, it seems

likely that the use of many médicinal plants

may hâve derived from the ingestion of rarely

eaten or fall-back foods (consumed in periods

of major food shortage) with supportive

médicinal properties [44]. In many cases

below, herbal medicines for veterinary use can

be given or prepared in whole herb or herb

extracts, as shown in Fig.1

Fig 1. The Use of herbal medicine in veterinary

Although most veterinary dosage forms contain

the same drug as human dosage forms, some

veterinary preparation includes drugs that are

not widely used in humans. 3. These reasons do

not impact the science used to develop such

dosage forms, but they heavily impact the

outcomes such as the size, shape, volume

administered, etc., of the dosage form.

Veterinary pharmaceuticals play an important

role in human and animal health [45,46].

Dosage forms are how drug molecules or plant

parts are delivered to sites of action within the

body [47]. The routes for which herbal dosage

forms may be administered include oral, rectal,

topical, parenteral, respiratory, nasal,

ophthalmic, and otic, as shown in Fig 2.

Categorizing finished herbal products into

dosage forms will help define specific

protocols for quality control and stability

testing. Herbal medicinal products may be

designated as finished, labeled medicinal

products containing active ingredients aerial or

underground parts of plants, or other plant

material, or combinations thereof, whether in

the crude state or as plant preparations. Herbal

medicines may contain excipients in addition to

active ingredients. Medicines containing plant

materials combined with chemically defined

active substances, including chemically

defined, isolated plants, are not considered

herbal medicines. Finished herbal products or

herbal drug preparations are varied, and various

solvents may be used for their extraction,

distillation, expression, fractionation,

purification, concentration, or fermentation.

These include comminuted or powdered herbal

drugs, tinctures, extracts, essential oils,

expressed juices, and processed exudates.

Factor Involved in Deciding route of

administration: Concentration of drug needed,

the site where drug required, time of action,

duration of action, circumstances of action site,

safety, and cost [48].

Pharmaceutical quality is an essential

ingredient of product safety and requires the

product to be manufactured according to

specific standards of purity and consistency.

These standards apply throughout the

production and formulation process. Stability

studies ensure that the product retains its

potency, efficacy, and safety for the full

duration of the shelf-life 2. However,

veterinarians and pharmacists must be aware of

potential incompatibilities and practices that

may interfere with the drug’s stability, purity,

and potency 3.

3.3 Unique aspects Veterinary Dosage Form

Animal drug dosage forms have their

requirements & characteristics based on the

unique aspects of mammal & avian physiology.

Many drugs used in veterinary medicine are not

used in human medicine, and therefore,

pharmacists may not know their attributes. The

pharmacist who desires to practice in this area

should undertake self-study to learn the

chemical, biochemical (metabolism),

pharmacological (mechanisms), therapeutic

(clinical outcomes), and pharmaceutical

(dosage forms) and pharmacokinetic

characteristics of these compounds. Some

dosage forms are specially designed for

animals (e.g., Ear tags, collars, and darts). Most

drug delivery systems (including nano-carriers

Fig 2 Dosage forms of herbal medicinal products

and controlled drug delivery systems) are

common among animals and humans 9.

Flavors that animals prefer to include Dog

prefers Beef, Chicken, Cheddar Cheese,

Molasses, Peanut Butter, Liver, Raspberry,

Strawberry. Cat prefers Tuna, Chicken, Beef,

Cheddar Cheese, Peanut Butter, Liver,

Butterscotch. Bird prefers Grape, Mandarin

Orange, Tutti-Frutti, Molasses, Pina Colada.

Horse prefers Apple, Creamy Caramel,

Molasses, Licorice, Cherry. Rabbit prefers

Banana Ferret prefers Bubble Gum, Molasses.

Gerbils prefers Mandarin Orange, Tutti-frutti 9.

In general there are similarities between human

and animal preparations, but there are some that

are specific to animals 3.

• medicated powders for administration in

drinking water (herd health);

• drenches (a large volume of aqueous

suspension or solution containing the API that

is pumped into the animal’s rumen);

• medicated articles (a formulation intended for

administration in feed)

• rumen bolus (a large tablet designed for

administration in ruminants and which can

provide either immediate drug release or

remain in the rumen for a prolonged duration of

time to provide extended drug release).

4. Herbal drugs used in veterinary

practice

For veterinary use, quality specifications for

veterinary herbal medicines need to be

developed. There is a need for validation of

traditional claims systems (detailed

pharmacognostic, phytochemical, and

pharmacological studies, etc.) and evaluation

of the safety of plant models for their

development and use as veterinary drugs 49.

Standardization of veterinary herbal medicines

is needed to determine their quality,

consistency, and reproducibility. This stage is

to ensure that one or more of the main

phytochemical ingredients of veterinary herbal

medicines or other ingredients are present in the

specified amount. Quality control is applied for

batch-wise consistency, dose uniformity,

stability, and to detect

contamination/counterfeiting. Identifying the

biologically active compounds in herbs is very

important for quality control and for

determining the dosage of plant-based drugs.

When used in small amounts, certain plants are

useful as veterinary drugs, while in large

quantities they are toxic 49,50.

Standardization of herbal medicines is a

complicated process because these medicines

contain complex mixtures of different

compounds. Thus, the herbs responsible for the

medicinal effect are often unknown.

Knowledge of the physicochemical properties

of herbal medicines, along with other

preformulation data, is necessary for the

standardization and validation of active

constituents. Various chemical, spectroscopic,

and biological methods are also employed for

the standardization. Some examples include

infrared spectroscopy, liquid chromatography,

high-performance thin-layer chromatography

(HPTLC), nuclear magnetic resonance, mass

spectroscopy, etc 51–53.

Good manufacturing practices (GMP) is a

system that ensures that the products

manufactured are consistently produced are

controlled according to quality standards and

that they minimize those risks involved in the

production that cannot be eliminated through

testing of the final product. GMP covers all

aspects of production from the starting

materials, premises, and equipment to the

staff's training, safety measures, and personal

hygiene. It also ensures that proper standard

operating procedures are followed; the work

environment is controlled; quality assurance,

packaging, and labeling are done according to

the requirements 48,51.

Currently used for veterinary medicine, many

use drugs commonly used in humans. Drug

administration is done by adjusting the dose.

The proper translation of drug doses from one

animal species to another and the translation of

animal doses to human doses are both critical

to the safety and efficacy of drugs. The

equivalence to human doses was calculated

using the formula shown in Table 2 54,55.

Table 2 Conversion of human equivalent dose

to animal dose 55

Species

Weight

(kg)

BSA

(mg/m2)

factor

Human

Adult

1.6

Child

0.8

Baboon

0.6

Dog

0.5

Monkey

0.3

0.24

Rabbit

1.8

0.15

Guinea Pig

0.4

0.05

Rat

0.15

0.025

Hamster

0.008

0.02

Mouse

0.02

0.007

5. Perspective

Traditional veterinary knowledge is passed

down from generation to generation. The

disconnect between traditional veterinary

knowledge in the current generation has led to

its extinction. To overcome the extinction of

local wisdom in veterinary medicine, there

must be studies that are continuously seeking

from various sources. 56,57.

Future developments will apply technology

that is currently developing and helps in the

world of health by implementing an intelligent

drug delivery system. One practical function of

nanotechnology in medicine, which is currently

being developed, involves using nanoparticles

to administer drugs or other constituents to

specific cell types 58. Nanoparticles were

developed to deliver hormones, antibiotics,

genes, anticancer drugs, anti-inflammatory

drugs, antigens, and growth factors. The system

can be used for target delivery of different

cargo molecules to increase drug

bioavailability, maintain drug effect on specific

target tissues/organs, solubilize drug, and

improve drug stability against degradation 39.

The others is developing a drug into a long-

acting delivery system include reducing dose

frequency to improve patient compliance or

enhancing the efficiency of therapy and thereby

improving the health of the patient. In contrast,

in the veterinary field, the major reasons for

developing a drug into a long-acting drug

delivery system is to minimize animal handling

to reduce the stress to animals from repeated

administration and to reduce the cost of

treatment in terms of money and time spent by

the end-user on drug administration. The

veterinary area offers opportunities to develop

novel controlled-release drug delivery

technologies adapted to livestock or companion

animal health needs 39.

The administration of drugs through the skin is

a non-invasive, convenient, and comfortable

way to administer drugs without trauma or risk

of infection This procedure avoids gastric

metabolism and the first-pass effect through the

liver found in the oral treatment. It also reduces

side effects and increases the interval between

administrations, thereby facilitating treatment

compliance from pet owners (Prausnitz 59)

6. Conclusion

The development of veterinary herbal medicine

will be a new solution to overcome the

challenge of antibiotic resistance to increase

animal production. In some cases, it also

improves profitability in meat production or

meets the safety criteria related to drug

residues. Veterinary medicice play a role in

restoring animal health, which will have an

impact on human welfare. To develop

traditional preparations, the latest

pharmaceutical knowledge is needed, to make

effective and efficient preparations. This

development requires special consideration in

making veterinary preparations. As in

traditional medicine for humans, to be able to

progress, it needs special attention for its

development from the government,

researchers, business. There must be

development of veterinary herbal medicines

that can be sold at relatively low prices

compared to modern medicines. If herbal

veterinary medicines lose their advantage over

allopathic medicines

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