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Sublingual route for systemic drug delivery

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Drug delivery via the oral mucous membrane is considered to be a promising alternative to the oral route. Sublingual route is a rapid onset of action and better patient compliance than orally ingested tablets. Sublingual literally meaning is “under the tongue”, administrating substance via mouth in such a way that the substance is rapidly absorbed via blood vessels under tongue. The portion of drug absorbed through the sublingual blood vessels bypasses the hepatic first‐pass metabolic processes giving acceptable bioavailability. Sublingual technology is convenient for dosing in geriatric, pediatric and psychiatric patients with dysphagia. Sublingual drug delivery shows fast therapeutic action than orally ingested drugs with fewer side effects. This review highlights advantages, disadvantages, different sublingual Gland, sublingual formulation such as tablets, films drops, sprays etc, evaluation parameters. Keywords: Sublingual delivery, dysphagia, sublingual gland, improved bioavailability, evaluations.
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Pawar et al Journal of Drug Delivery & Therapeutics. 2018; 8(6-s):340-343
ISSN: 2250-1177 [340] CODEN (USA): JDDTAO
Available online on 15.12.2018 at http://jddtonline.info
Journal of Drug Delivery and Therapeutics
Open Access to Pharmaceutical and Medical Research
© 2011-18, publisher and licensee JDDT, This is an Open Access article which permits
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Open Access Review Article
Sublingual route for systemic drug delivery
Pawar Poonam P*1, Ghorpade Hemant S.2, Kokane Bhavana A.3
*1MABD Diploma College of Pharmacy, Yeola, Nasik (MH), India.
2Production Department, FDC Ltd. Waluj, Aurangabad(MH), India.
3 MABD Diploma College of Pharmacy, Yeola, Nasik (MH), India.
ABSTRACT
Drug delivery via the oral mucous membrane is considered to be a promising alternative to the oral route. Sublingual route is a rapid onset
of action and better patient compliance than orally ingested tablets. Sublingual literally meaning is “under the tongue”, administrating
substance via mouth in such a way that the substance is rapidly absorbed via blood vessels under tongue. The portion of drug absorbed
through the sublingual blood vessels bypasses the hepatic first‐pass metabolic processes giving acceptable bioavailability. Sublingual
technology is convenient for dosing in geriatric, pediatric and psychiatric patients with dysphagia. Sublingual drug delivery shows fast
therapeutic action than orally ingested drugs with fewer side effects. This review highlights advantages, disadvantages, different sublingual
Gland, sublingual formulation such as tablets, films drops, sprays etc, evaluation parameters.
Keywords: Sublingual delivery, dysphagia, sublingual gland, improved bioavailability, evaluations.
Article Info: Received 18 Oct, 2018; Review Completed 30 Nov 2018; Accepted 01 Dec 2018; Available online 15 Dec 2018
Cite this article as:
Pawar PP, Ghorpade HS, Kokane BA, Sublingual route for systemic drug delivery, Journal of Drug Delivery and
Therapeutics. 2018; 8(6-s):340-343 DOI: http://dx.doi.org/10.22270/jddt.v8i6-s.2097
*Address for Correspondence:
Poonam P Pawar, MABD Diploma College of Pharmacy, Babhulgaon, Yeola, Nasik (MH), India.
INTRODUCTION
Sublingual Drug Delivery
Definition
“Systemic delivery of drugs through the mucosal
membranes lining the floor of the mouth to the systemic
circulation.”
The systemic drug delivery provide immediate onset of
pharmacological effects through the sublingual route.
Dysphasia (Difficulty in swallowing) is common problem of
all age groups or on reduced liquid intake have difficulties
in swallowing the solid dosage forms. Sublingual
administration of the drug means placement of drug i.e.
dosage form under the tongue & drug reaches directly into
the systemic circulation.1, 2
Sublingual drug delivery is alternative approach to the
enteral drug delivery. It avoids first pass metabolism in
liver and gastric acid hydrolysis of drugs therefore shows
in increase in oral bioavailability of drugs.
Principles
When a chemical comes in contact with mucous membrane
beneath the tongue, it diffuse
through it because of connective tissue beneath the
epithelium contains a profusion of capillaries, the
substance then diffuses into them and enters the venous
circulation.
Drug solutes are rapidly absorbed into reticulated vein
which is lies underneath the oral mucosa & transported
through the facial veins, internal jugular vein &
brachiocephalic vein & then enter in systemic circulation.3,4
ADVANTAGES OF SUBLINGUAL DRUG DELIVERY5-7
It produces immediate systemic effect by enabling the
drug absorbed quickly or directly through mucosal
lining of the mouth beneath the tongue.
Dose gets reduced.
Onset of action is very fast.
Improved bioavailability.
Fewer side effects.
Effective in disease like nausea, vomiting, migraine,
schizophrenia.
No need of water for administering tablet.
Ease of drug administration gets increased.
Sublingual area is much more permeable than buccal
area.
Bypass GI tract and hepatic portal system and avoid
hepatic first pass metabolism due to this
bioavailability of drug get increase.
Rapid absorption due to high vascularization beneath
the tongue.
pH in the mouth is relatively neutral so drug will be
more stable.
Improved patient compliance.
Pawar et al Journal of Drug Delivery & Therapeutics. 2018; 8(6-s):340-343
ISSN: 2250-1177 [341] CODEN (USA): JDDTAO
DISADVANTAGES OF SUBLINGUAL DRUG
DELIVERY5-7
Unsuitable for uncooperative or unconscious patients.
Unsuitable for bitter drugs.
Poor Patient compliance.
Eating, drinking, and smoking are not allowed.
Administration of highly ionic drug is not allowed.
Holding the dose in mouth is inconvenient, if any is
swallowed that portion must be treated as an oral
dose and subjected to first pass metabolism.
SUBLINGUAL GLAND
Salivary glands which are present in the floor of the mouth
underneath the tongue. They are also known as sublingual
glands. They produce mucin in turn produces saliva. The
interior area of the mouth remains lubricated due to
production of the saliva by the glands, which is necessary
for chewing and food swallowing. Due to low secretion of
the saliva it can create problem in swallowing the food and
potential for food lodge in the throat increases. The
absorption occurs by transfer of the drug from its site of
administration into systemic circulation, so it can be said
that absorption is directly proportional layer thickness.
Due to high permeability and rich blood supply, the
sublingual route can produce rapid onset of action so the
drug with short delivery period can be delivered and dose
regimen is frequent. The drug gets diluted in the saliva and
from there the drug is adsorbed across the oral cavity.8
SUBLINGUAL ABSORPTION
Mechanism of sublingual absorption
Sublingual administration drug solutes are rapidly
absorbed into the reticulated vein, which lies underneath
the oral mucosa and transported through the facial veins,
internal jugular vein and are then drained into the
systemic circulation. Upon sublingual administration drug
reaches directly into the blood stream through the ventral
surface of the tongue and floor of the mouth. The main
mechanism for the absorption of the drug into oral mucosa
is via passive diffusion into the pilonidal membrane.5
Factors affecting on sublingual absorption 4, 8
Solubility in Salivary Secretion
In addition to high lipid solubility, the drug should be
soluble in aqueous buccal fluids i.e. biphasic solubility of
drug is necessary for absorption.
Binding to Oral Mucosa
Systemic availability of drugs that bind to oral mucosa is
poor.
pH and pKa of The Saliva
As the mean pH of the saliva is 6.0, this pH favors the
absorption of drugs which remain unionized. Also, the
absorption of the drugs through the oral mucosa occurs if
the pKa is greater than 2 for an acid and less than 10 for a
base.
Lipophilicity of Drug
For a drug to be absorbed completely through sublingual
route, the drug must have slightly higher lipid solubility
than that required for GI absorption is necessary for
passive permeation.
Thickness of Oral Epithelium
As the thickness of sublingual epithelium is 100‐200 μm
which is less as compared to buccal thickness. So the
absorption of drugs is faster due to thinner epithelium and
also the immersion of drug in smaller volume of saliva.
DRUGS FOR SUBLINGUAL ADMINISTRATION8-10
Sublingual drug administration is applied in the field of
cardiovascular drugs, steroids, some barbiturates and
enzymes. The drugs with dose less than 20 mg are suitable
for sublingual drug delivery system. It has been a
developing field in the administration of many vitamins
and minerals which are found to be readily and thoroughly
absorbed by this method. Sublingually absorbed nutrition,
which avoids exposure to the gastric system and liver,
means direct nutritional benefits, particularly important
for sufferers of gastro‐intestinal difficulties such as ulcers,
hyperactive gut, coeliac disease, those with compromised
digestion, the elderly and invalids the nutritional benefit is
independent of gastro‐intestinal influences. Examples of
drugs administered by this route include antianginal like
nitrites and nitrates, anti hypertensive like nifedipine,
analgesics like morphine and bronchodilators like
fenoterol. Certain steroids like estradiol and peptides like
oxytocin can also be administered e.g. fentanyl
SUBLINGUAL FORMULATIONS11-15
Sublingual Tablets
Sublingual Films
Multipurpose tablets
Sublingual drops
Sublingual spray
Lozenge
Effervescent sublingual tablets
Sublingual Tablets
“Sublingual tablets are solid unit dosage form meant for
placement under the tongue to produce immediate action
by avoiding the first pass effect of drug by liver.
The tablets are usually small and flat, compressed lightly to
keep them soft. The tablet must dissolve quickly allowing
the API to be absorbed quickly. It is designed to dissolve in
small quantity of saliva. After the tablet is placed in the
mouth below the tongue, the patient should avoid eating,
drinking, smoking and possibly talking in order to keep the
tablet in place. Swallowing of saliva should also be avoided
since the saliva may contain dissolved drug. Bland
excipients are used to avoid salivary stimulation.
Nitroglycerine tablets and Ondansetron tablets (zopran)
are the examples of sublingual tablets.
Sublingual Films
Mouth dissolving films or strip, a new drug delivery
system for the oral delivery of the drugs, was developed
based on the technology of the transdermal patch. The
delivery system consists of a very thin oral strip, which is
simply placed on the patient’s tongue or any oral mucosal
tissue, instantly wet by saliva the film rapidly hydrates and
adheres onto the site of application. It then rapidly
disintegrates and dissolves to release the medication for
oromucosal absorption or with formula modifications, will
maintain the quick-dissolving aspects allow for
gastrointestinal absorption to be achieved when
swallowed. Sublingual strips are similar to tablets in that
they easily melt in the mouth and dissolve rapidly.
Suboxone is an example of medication that comes in a
sublingual strip.
Pawar et al Journal of Drug Delivery & Therapeutics. 2018; 8(6-s):340-343
ISSN: 2250-1177 [342] CODEN (USA): JDDTAO
Multi-Purpose Tablets
Soluble tablets for either oral or sublingual administration,
often also suitable for preparation of injections, Hydrostat
(hydromorphone) and a number of brands of morphine
tablets and cubes.
Sublingual Drops
Concentrated solutions to be dropped under the tongue, as
with some nicocodeine cough preparatations.
Sublingual Spray
Spray for the tongue; certain human and veterinary drugs
are dispensed as such.
Lozenge
Effects a metred and patient-controlled-rate combination
of sublingual, buccal, and oral administration, as with the
Actiq fentanyl lozenge-on-a-stick (lollipop).
Effervescent Sublingual Tablets
This method drives the drug through the mucous
membranes much faster (this is the case in the stomach
with carbonated or effervescent liquids as well) and is
used in the Fentora fentanyl tablet.
EVALUATION PARAMETERS16-22
General Appearance
The general appearance of a tablet, its visual identity and
over all "elegance" is essential for consumer acceptance.
Include in are tablet's size, shape, color, presence or
absence of an odor, taste, surface texture, physical flaws
and consistency and legibility of any identifying marking.
Size and Shape
The size and shape of the tablet can be dimensionally
described, monitored and controlled.
Tablet Thickness
Tablet thickness is an important characteristic in
reproducing appearance and also in counting by using
filling equipment. Some filling equipment utilizes the
uniform thickness of the tablets as accounting mechanism.
Wetting Time
Using this test, the time required for moisture to penetrate
the tablet completely is measured and possibly represents
the time required to release drug in the presence of minute
volumes of saliva.
A piece of tissue paper (12 cm X 10.75 cm) folded twice
was placed in a small Petri dish (ID = 6.5 cm) containing 6
ml of Sorenson's buffer pH 6.8. A tablet was put on the
paper, and the time for complete wetting was measured.
Three trials for each batch and the standard deviation
were also determined.
Uniformity of Weight
I.P. procedure for uniformity of weight was followed,
twenty tablets were taken and their weight was
determined individually and collectively on a digital
weighing balance. The average weight of one tablet was
determined from the collective weight.
Table 1: IP limit for weight variation
Avg. Weight of Tablet
% Variation Allowed
80mg or less
10
60mg but < 250mg
7.5
250mg or more
5
Friability
It is measured of mechanical strength of tablets. Roche
friabilator can be used to determine the friability by
following procedure. A preweighed tablet was placed in
the friabilator. Friabilator consist of a plastic-chamber that
revolves at 25 rpm, dropping those tablets at a distance of
6 inches with each revolution. The tablets were rotated in
the friabilator for at least 4 minutes. At the end of test
tablets were dusted and reweighed, the loss in the weight
of tablet is the measure of friability and is expressed in
percentage as %Friability = loss in weight / Initial weight x
100.
Tablet Hardness
Hardness of tablet is defined as the force applied across the
diameter of the tablet in the order to break the tablet. The
resistance of the tablet to chipping, abrasion or breakage
under condition of storage transformation and handling
before usage depends on its hardness. Hardness of the
tablet of each formulation was determined using Monsanto
Hardness tester.
In-Vitro Dispersion Time
In-vitro dispersion time can be measured by dropping a
tablet in a beaker containing 50 ml of Sorenson's buffer pH
6.8.
In-Vitro Disintegration Test
The test can be carry out on 6 tablets using the apparatus
specified in I.P. 1996 distilled water at 37ºC ± 2ºC was used
as a disintegration media and the time in second taken for
complete disintegration of the tablet with no palable mass
remaining in the apparatus measure in seconds.
CONCLUSION
Sublingual drug delivery has been used for formulation of
many drugs with view point of rapid drug release and
quick onset of action. Sublingual products were developed
to overcome the difficulty in swallowing conventional
tablet, among pediatric, geriatric and psychiatric patients
with dysphagia. The potential for such dosage forms is
promising because strong market acceptance and patient
demand. Peak blood levels of most products administered
sublingually are achieved within few minutes, which is
generally much faster than when those same drugs are
ingested orally. Sublingual absorption is efficient. The
percent of each dose absorbed is generally higher than that
achieved by means of oral ingestion. Various types of
sublingual dosage forms are available in market like
tablets, films, sprays, Drops, Lozenge etc.
Pawar et al Journal of Drug Delivery & Therapeutics. 2018; 8(6-s):340-343
ISSN: 2250-1177 [343] CODEN (USA): JDDTAO
REFERENCES
1. Bind AK, Gnanarajan G, Kothiyal P, Sublingual route for
systemic drug delivery: A Pharmaceutical Review,
International Journal of Drug Research and Technology,
2013; 3(2):31-36.
2. Singh B, Gupta S, Kumar A, Fabrication and evaluation of
sublingual tablets of telmisartan using different
superdisintegrants: formulation and evaluation, International
Journal of Pharmacy and Pharmaceutical Research, 2015;
3(1):201-218.
3. Pawar PP, Gaikwad SS, Patil PB, Design and development of
sublingual tablets of ondansetron hydrochloride: formulation
and evaluation, World Journal of Pharmacy and
Pharmaceutical Sciences, 2016; 5(12):733-745.
4. Shah S, Badola A, Kothiyal P, Sublingual tablets an overview:
A pharmaceuitical review, Indian Journal of Pharmaceutical
and Biological Research, 2016; 4(2):20-26.
5. Singh M, Chitranshi N, Singh AP, Arora V, Siddiqi AW, An
overview on fast disintegrating sublingual tablets: A
pharmaceuitical review International Journal of drug
delivery, 2012; 4(4):407-417.
6. Narang N, Sharma J, Sublingual mucosa as a route for
systemic drug delivery: A pharmaceuitical review,
International Journal of Pharmacy and Pharmaceutical
Sciences, 2011; 3(2):18-22.
7. Patel P, Makwana S, Jobanputra U et al, Sublingual route for
systemic delivery of ondansetron: A pharmaceuitical review,
International Journal of Drug Development and Research,
2011; 3(4):36-40.
8. Sarkhejiya NA, Patel VP, Pandya DJ, Sublingual delivery A
promising approach to improve bioavailability: A
pharmaceuitical review, Pharma Sciences an International
Journal of Pharmaceutical Sciences, 2013; 4(2):3870-3889.
9. Kavitha K, Subramaniam K, Hui BJ, et al, Potential drug
candidate for fast dissolving drug delivery: A pharmaceuitical
review, Research Journal of Pharmaceutical, Biological and
Chemical Sciences, 2013; 4(4):1510-1526.
10. Vilayat AS, Mohammad A, Considerations in developing
sublingual tablets: A pharmaceuitical review, PharmTech
Advancing Development and Manufacturing, 2014; 38(11).
11. Patel KN, Pancholi SS, Sublingual route for systemic drug
delivery: A pharmaceuitical review, International Journal of
Research in Pharmaceutical and biomedical Sciences, 2012;
3(2):913-923.
12. Arya A, Chandra A, Sharma V, Pathak K, Fast dissolving oral
film an innovative drug delivery system and dosage form: A
pharmaceuitical review, International Journal of ChemTech
Research, 2010; 2(1):576-583.
13. Kapadia YD, Sodha HP, Patel VP, Formulation development
and evaluation of sublingual film of asenapine maleate:
formulation and evaluation, Pharma Science Monitor an
international Journal of Pharmaceutical Science, 2013;
4(3):190-209.
14. Siddiqui N, Garg G, Sharma PK, A novel approach in oral fast
dissolving drug delivery system and their patents: A
pharmaceuitical review, Advances in Biological research,
2011; 5(6):291-303.
15. Lachman L, Liebermann HA, Kanig JL.The Theory and
Practice of Industrial Pharmacy, 3rd ed. Mumbai: Varghese
Publishing House1990. P. 479-488.
16. Indian Pharmacopoeia, Controller of publications, Govt. of
India Ministry of health and family welfare, New Delhi, 1996.
P. A-147.
17. United State Pharmacopoeia 30NF25, the official compendia
of standards, Asian edition, United States Pharmacopoeial
convection Inc. Rockville MD 2009. P. 276-383,617-658,806-
807,817, 1764, 2492-2495.
18. Pethe AM, Salunkhe SP, Formulation and evaluation of
mucoadhesive buccal tablet of simvastatin: formulation and
evaluation, International Journal of Pharma and Bio Science,
2014, 5(3), 268-278.
19. Deshmukh G, Ruikar D, Seth AK et al, Formulation and
development of lamotrigine fast disintegrating tablet:
formulation and evaluation, Pharma Science Monitor an
International Journal of Pharmaceutical Sciences, 2011;
2(2):S7-S15.
20. Nagar P, Singh K, Chauhan I et al, Orally disintegrating
tablets: Formulation, preparation techniques and evaluation:
A pharmaceutical review, Journal of Applied Pharamaceutical
Science, 2011; 1(4):35-45.
21. Gaikwad SS, Jadhav AA, Chavan MK et al, Design and In-vitro
evaluation of sublingual tablets of timolol maleate:
formulation and evaluation, Bentham Science Applied clinical
Research, Clinical Trials and Regulatory Affairs, 2016;
3(1):56-63.
22. Senthil A, Navinchandra CP, Jose J, Mahim MM, Ravajibhai SY.
Preparation and evaluation of timolol maleate mucoadhesive
buccal tablets: formulation and evaluation, International
Research Journal of Pharmacy, 2012; 3(3):292-297.
... The main advantage over the oral route is that buccal/sublingual administration provides a quicker onset of drug action, and higher bioavailabilities are often achieved. Moreover, buccal/sublingual administration can be used when patients are experiencing nausea, vomiting, or dysphagia [14,15]. Nevertheless, this route has some limitations, as it cannot be used in unconscious patients and patients tend not to administer the formulation correctly if it is bitter or has an unpleasant taste [15]. ...
... Moreover, buccal/sublingual administration can be used when patients are experiencing nausea, vomiting, or dysphagia [14,15]. Nevertheless, this route has some limitations, as it cannot be used in unconscious patients and patients tend not to administer the formulation correctly if it is bitter or has an unpleasant taste [15]. ...
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... 30 The intranasal route, however, had a faster onset of drug action, which is consistet with findings from AlRakaf et al, 19 Shanmugaavel et al, 31 and Kılınç et al 32 Although the rich blood supply of the sublingual mucosa allows for the rapid absorption of drugs directly into the systemic circulation, the absorption seems to be affected by various factors such as residence time, which is the time that the drug remains in contact with the mucosal surface, local pH, salivary flow, and the physicochemical characteristics of the drug administered and of the chosen site of action. 33 On the other hand, Al Ghananaeem 34 reported that both intranasal and sublingual routes offer rapid onset since they both avoid what is known as hepatic first-pass metabolism allowing the drug to be absorbed directly into the systemic circulation. Concerning the anxiety level, the results of the present study did not show a significant difference in the anxiety scores between baseline and local anesthesia administration in both groups. ...
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... [65] Sublingual route In sublingual administration, the therapeutic molecule is placed under the tongue without the application of water and are allowed to disintegrate, before being absorbed by lymphatic vessels. [66] The sublingual or buccal route is an attractive approach, characteristic of limited proteolytic activity, and ease of accessibility. [38] Typically, this route has a surface area of 200 cm 2 , pH of 6.2-7.4, ...
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... There are several advantages of sublingual administration, e.g., rapid absorption and fast onset of action, increase bioavailability, easy to use, avoid first-pass metabolism, etc. (Pawar, Ghorpade, & Kokane, 2018). However, the sublingual drops exhibited less accurate dosing style, the suitable administration technique highly affected the dose accuracy. ...
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... Sublingual means "under the tongue", the sublingual tablet is administered in such way that it gets rapidly disintegrate, dissolve in patient's mouth without chewing or water administration and absorbed rapidly through the blood vessels present below the tongue. Therefore the drug gets enter into systemic circulation to give on set of action by avoiding the first pass metabolism and degradation [8][9][10]. This route is most suitable for acid labile drugs and convenient for paediatrics, geriatrics, and psychiatric patients and also patients with difficulties in swallowing (dysphagia), and in situations where water is not available [11]. ...
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