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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
Journal of Drug Delivery and Therapeutics
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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.
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:
*Address for Correspondence:
Poonam P Pawar, MABD Diploma College of Pharmacy, Babhulgaon, Yeola, Nasik (MH), India.
Sublingual Drug Delivery
“Systemic delivery of drugs through the mucosal
membranes lining the floor of the mouth to the systemic
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.
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
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
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,
No need of water for administering tablet.
Ease of drug administration gets increased.
Sublingual area is much more permeable than buccal
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
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.
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
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
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
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.
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 Tablets
Sublingual Films
Multipurpose tablets
Sublingual drops
Sublingual spray
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.
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.
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
60mg but < 250mg
250mg or more
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
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
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.
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
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... 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]. ...
Over the last couple of decades, the popularity of long-acting drug delivery systems (LADDSs) has increased significantly. This type of drug delivery system presents several advantages over conventional routes such as oral route. LADDSs can be injected/implanted into the body of the patient for providing prolonged unattended drug release. This type of system is an ideal candidate for the treatment of chronic conditions that require constant drug uptake. Moreover, this type of device can be used for the local delivery of drugs. This chapter provides an overview of the current clinical needs and applications of LADDS. Moreover, the potential future applications of this type of technology are discussed.
... 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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Background Most of children suffer from dental anxiety during dental treatment. Conscious sedation is used to alleviate anxiety and enhance child’s cooperation. Aim This study aimed to compare the efficacy of intranasal versus sublingual dexmedetomidine. Design: Forty-two healthy, uncooperative children participated in the study. They were divided randomly into two groups, group I received intranasal dexmedetomidine in the first visit and group II received sublingual dexmedetomidine, while at the second visit, the alternate route was implemented in a cross-over design. Child’s acceptance to drug administration method was assessed using four-point rating scale. Time until optimum sedation was measured. Anxiety during local anesthesia administration was scored using Venham’s rating scale. Post-operative response was recorded through Vernon et al questionnaire. Results Sublingual route was better accepted than intranasal route, while the latter acted faster. Within groups’ comparison, no statistically significant difference in anxiety scores was found between base line and local anesthesia administration. Similarly, no significant difference in the anxiety scores was found between both groups or between genders during local anesthesia administration. Conclusions Both routes prevented the increase in anxiety scores equally during local anesthesia and do not have negative effect on postoperative behavior of children.
... [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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Delivery of food and drug molecules is a challenging field of research with growing interests. Due to concerns on solubility, stability, and bioavailability, numerous techniques have been explored to identify effective and sustainable approaches. The large surface area and wide blood supply made the lungs a prominent route for the delivery of therapeutic molecules. Several drug molecules have been effectively delivered through the pulmonary route, and this review focuses on the pulmonary delivery of food-derived therapeutic molecules through aerosols. Various methods have been used to fabricate aerosols; their mechanism of deposition and absorption in the lungs involves intricacies in terms of a range of factors including their physical and aerodynamic properties, apart from the conditions of the body. This review attempts to elaborate on these aspects, apart from providing a status report on the current scenario of delivering therapeutic molecules through the pulmonary route. Importantly, highlighting regulatory aspects, challenges associated with the delivery of food-derived molecules such as aerosols are presented, giving lead for directions for future research.
... 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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This work sought to evaluate the stability of cannabis sublingual drops using high-performance liquid chromatography. The cannabis extract was dissolved in different types of vegetable oil–four types of mixed vegetable oils and 11 types of single vegetable oil. They were stored in the dark at 4 °C and 30 °C for 90 days. The contents of main cannabinoids (cannabidiol, tetrahydrocannabinol, and cannabinol) were analyzed and compared with the contents at the initial time. Results showed that almost all of the vegetable oil types provided the formulation with a shelf-life (remained cannabidiol and tetrahydrocannabinol ≥ 90%) of more than 60 days but less than 90 days at 30 °C. Storage of cannabis sublingual drops at 4 °C provided more stable formulations than at 30 °C. The formulations with the shelf-life of more than 90 days were found when the seven vegetable oils, including mixed oil (no.1), mixed oil (no.3), sesame oil, rice bran oil, olive oil (no.1), coconut oil (no.1), and coconut oil (no.2) were used. In summary, the seven vegetable oil types can be selected as a vehicle to prepare the cannabis sublingual drops due to they could stabilize cannabinoids content.
... 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]. ...
... The buccal lining is also one of the robust lining of human body and can be used for systemic drug delivery [56]. As compared to other oral linings like sublingual route (floor of the mouth) [57], gingival route (gums) [58], linings around the lips, palatal mucosal route etc. [59], The buccal lining have different permeability to selective drugs, different anatomy, and desired length in order to keep the hold on the drug delivery dosage form like patches, tablets, semi-solid dosage form [60]. This buccal lining can be used not only for local drug delivery but can also be used for systemic drug delivery with better bioavailability. ...
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Mucoadhesive dosage forms may be intended for facilitation of prolonged retention time at the application site hence providing drug release in a controlled rate for enhanced improvement of therapeutic activity and its outcome. The buccal mucosa has been investigated for systemic drug delivery and local drug treatment or therapy that is subjected to first pass metabolism. The applicability of bio-adhesion approach in buccal drug delivery proved great therapeutic potential to overcome the limitation of conventional buccal drug delivery. The delivery via buccal route using mucoadhesive biopolymers such as various natural gums e.g. carrageenans, gum karaya, gum arabic, locust bean gum, khaya gum, gum ghatti, albizia gum, guar gum, starch, cellulose, larch gum and pectin etc. and various thiolated and carboxymethylated polymers has been the subject of interest since the early 20th century. The present article is focused mainly on the oral mucosa, mechanism of drug permeation, and characteristics of the desired polymers, the manuscript then proceeds to cover the theories behind the adhesion of bioadhesive polymers to the mucosal epithelium followed by the factors affecting mucoadhesion. Further the author has also discussed on the new generation of mucoadhesive polymers and their properties, recent mucoadhesive formulations for enhanced buccal drug delivery, various marketed products and patent literature. Various online search engines and scientific journals were employed for the collection of literature and scientific data and information related to the topic using keywords like mucoadhesive polymers, buccal drug delivery, buccal patches, tablets, films, gels, powder from the year 2002 and above.
Biodegradation and biocompatibility are crucial for developing long-acting implantable drug delivery systems. Because of the prolonged biological residence of these implants, understanding of in vivo degradation and biocompatibility helps establish the commercial success of these implants. International Organization for Standardization has laid down various guidelines for the development and optimization of in vitro degradation studies. This chapter discusses multiple ISO guidelines and current research to understand the influence of different study parameters on biodegradation study. The chapter also summarizes the immunological consideration in the design and evaluation of long-acting implants.
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Allergic rhinitis (AR) is very common clinical condition and affects 10-40% of individuals worldwide. It has a substantial negative effect on patient's quality of life (QoL), sleep and daily activities. Various therapeutic classes are used for the management of allergic rhinitis. Among all the classes, H1 receptor antagonist is used as first line treatment. Many molecules belong to antihistamine class and on the basis of selectivity and its adverse effect it can be classified as first generation, second generation and novel second-generation antihistamine. Among all the molecules, Bilastine is a novel new second generation with selective peripheral, non-sedating, H1 antihistamine. Its affinity is also higher than the other antihistamine. It belongs to BCS class II drug which has less solubility and high permeability. So, for enhancement of solubility complexation technique is used and inclusion complex of Drug: HP-β-CD (1:2) was prepared by microwave irradiation method. Here great need arises to alter the route of administration of Bilastine for improving absorption and drug release pattern. As per the literature study, it can be concluded that Sublingual route offer immediate drug release directly into systemic circulation, results in rapid onset of action. In present study sublingual tablet of Bilastine is prepared by direct compression method. The effect of different superdisintegrants (SSG, CCS, Kyron T-314, Indion 414) in two different concentrations are examined for selection of best superdisintegrant. Result of check point batch F 10 suggested that tablet disintegrated within 50 sec. Similarly, in-vitro dissolution study showed 97.68 % drug release in 10 min.
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Asenapine Maleate has the half-life of 24 hour and bioavailability in the body is 35% due to first pass metabolism. The total daily dose of Asenapine Maleate is 5 mg (e.g., 5 mg once a day depending on meal patterns), hence it required frequent dosing. Sublingual Film of Asenapine Maleate was prepared for fast immediate release; improve bioavailability of drug and patient compliance. Different formulations were prepared by varying concentration of HPMC K4M and Ethanol: Water ratio by solvent casting method. The prepared formulations were evaluated for various parameters like thickness, tensile strength, folding endurance, % elongation, uniformity of weight, uniformity of drug content, in vitro dissolution study, disintegration time, stability study and drug excipients compatibility. In recent research work different concentration and Ethanol: Water ratios were used like 3.0%, 3.6%, 4.2% concentration and 30:20, 25:25, 20:30 Ethanol: Water ratio as used. The fast dissolving films were prepared by solvent casting method by using water-soluble polymer (Hydroxy Propyl Methyl Cellulose) taken through sublingual route. In this study PEG 400 is used as a plastsizer and ethanol, water is used as solvent. Concentration of water soluble polymer, PEG400 and Ethanol: Water ratio was optimized during preliminary studies. The results obtained showed no physicochemical incompatibility between the drug and the polymers. The prepared films were clear, transparent and smooth surface. Film containing Hydroxy Propyl Methyl Cellulose (3.00%) and Ethanol: Water (30:20) showed optimum performance against all other prepared formulations.
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Objective: The aim of the present study was to formulate fast disintegrating sublingual tablet of Timolol maleate (TM) for the potential emergency treatment of hypertension and also its potential to circumvent the first-pass metabolism and to improve its bioavailability. The demand of fast disintegrating sublingual tablet has been growing mainly for geriatric because of potential emergency treatment. Methods: The tablets were prepared by direct compression method by incorporation of two disintegrants Ac-di-sol and sodium starch glycolate (SSG). Importance behind the incorporation of super-disintegrant was to break the tablet in less time period which imparts release of drug. To study the effect of independent variables (Ac-di-sol and SSG) on disintegration time and in vitro drug release a 32 factorial design was utilized. Spectroscopic techniques like Ultraviolet (UV) and Fourier transform infrared spectroscopy (FTIR) were utilized for study physiochemical properties of drug. The formulations were evaluated for crushing strength, weight variation, thickness, friability, drug content, wetting time, In-vitro disintegration time, In-vitro dissolution study. Results: FTIR studies showed no evidence of interactions between drug and excipients. Formulation (F4) was compared with rest of the formulations for disintegration time, wetting time, % drug release, content uniformity which were found to be superior to others. The Disintegration time of all nine formulations was lies between 31 ± 1.732 s to 127 ± 8.718 s. Except the formulation (F1) and formulation (F9) all remaining formulations showed diffusional exponent (n) values of peppas model were lies between 0.624 - 0.9333 means that these formulations followed anomalous transport for release of drug which is a combination of diffusion and erosion. Conclusion: It was concluded that combination of super - disintegrants (Ac-di-sol: SSG in 3:4) showed significant (p < 0.001) disintegrating time, wetting time and water absorption ratio than the rest of the formulations. We successfully developed the sublingual tablet of TM with achieving desired objective.
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Fast-dissolving drug-delivery systems were first developed in the late 1970s as an alternative to tablets, capsules, and syrups for pediatric and geriatric patients who experience difficulties swallowing traditional oral solid-dosage forms. In response to this need, a variety of orally disintegrating tablet (ODT) formats were commercialized. Most ODT products were formulated to dissolve in less than one minute when exposed to saliva to form a solution that could then be more easily swallowed. Dissolvable oral thin films (OTFs) evolved over the past few years from the confection and oral care markets in the form of breath strips and became a novel and widely accepted form by consumers for delivering vitamins and personal care products. Companies with experience in the formulation of polymer coatings containing active pharmaceutical ingredients (APIs) for transdermal drug delivery capitalized on the opportunity to transition this technology to OTF formats. Today, OTFs are a proven and accepted technology for the systemic delivery of APIs for over-the-counter (OTC) medications and are in the early-to mid-development stages for prescription drugs.
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Fast dissolving oral films (FDOFs) are the most advanced form of oral solid dosage form due to more flexibility and comfort. It improve the efficacy of APIs by dissolving within minute in oral cavity after the contact with less saliva as compared to fast dissolving tablets, without chewing and no need of water for administration. The FDOFs place as an alternative in the market due to the consumer's preference for a fast-dissolving product over conventional tablets / capsules. The oral thin-film technology is still in the beginning stages and has bright future ahead because it fulfils all the need of patients. Eventually, film formulations having drug/s will be commercially launched using the oral film technology. However, for future growth point of view the oral thin film sector is well-positioned. In US market the OTC films of pain management and motion sickness are commercialized. More importantly, prescription OTFs have now been approved in US, EU and Japan which are the three major regions. These approved Rx films, have potential to dominate over other oral dosage forms of the same drugs. It seems that the value of the overall oral thin film market will grow significantly.
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Oral delivery is currently the gold standard in the pharmaceutical industry where it is regarded as the safest, most convenient and most economical method of drug delivery having the highest patient compliance. Formulation of a convenient dosage form for oral administration, by considering swallowing difficulty especially in case of geriatric and pediatric patient leads to poor patient compliance. To troubleshoot such problems a new dosage form known as orally disintegrating tablet (ODT), has been developed which rapidly disintegrate & dissolve in saliva and then easily swallowed without need of water which is a major benefit over conventional dosage form. In addition, patients suffering from dysphasia, motion sickness, repeated emesis and mental disorders prefer such preparation because they cannot swallow large quantity of water. Further, drugs exhibiting satisfactory absorption from the oral mucosa or intended for immediate pharmacological action can be advantageously formulated in such type of dosage form. The popularity and usefulness of the formulation resulted in development of several ODT technologies for preparation. The current article is focused on ideal characteristics, advantages and disadvantages, formulation aspects, formulation technologies, evaluation of products and future potential. Various marketed preparations along with numerous scientific advancements made so far in this avenue have also been discussed.
In present study mucoadhesive buccal tablet of simvastatin was prepared. Solubility of Simvastatin was enhanced by complexing Simvastatin with ß-CD in 1:2 molar concentrations. Six different formulations of tablets of Simvastatin containing the polymers in various combinations were prepared by direct compression method and characterized for swelling studies, % matrix erosion, surface pH, mucoadhesive properties, in-vitro release studies. All the formulations showed the satisfactory results bioadhesive performance, surface pH, physical& mechanical properties. The swelling index was proportional to carbopol content & other bio-adhesive polymer. The surface pH of all tablets was found to be satisfactory, close to neutral pH; hence, buccal cavity irritation should not occur with these tablets. Drug release and drug diffusion from the tablets were depended on the ratio and type of the polymer used in the formulation. Tablets containing Carbopol and HPMC K100 in the ratio of 4:1 had the maximum percentage of in-vitro drug release for 7h. The formulation F 4was optimized based on good bioadhesive strength (45 ± 0.55 g) and sustained in vitro drug release (65.96 % for 7h). The chosen tablet containing 10 mg of simvastatin performed 7h sustained drug release with desired therapeutic concentration.
Researchers throughout the world are focusing intensively on the methods for the development of new drug delivery systems to enhance patient's compliance. The oral route however still remained as the best administration route of therapeutic agents for its ease of ingestion, pain avoidance and versatility. Hence, fast dissolving tablets become an emerging trend in the pharmaceutical industry. Fast dissolving tablets are ideal for all types of people, including for people who have swallowing difficulties, paediatric, geriatric, and bedridden patients. It is also for active patients who are busy, travelling and may not have access to water. Fast dissolving tablets are also known as orodispersible tablets, mouth-dissolving tablets, orally disintegrating tablets, melt-in mouth tablets, rapimelts, porous tablets, quick dissolving etc. This type of tablets disintegrates quickly once introduced into the mouth in the absence of additional water for easy administration of active pharmaceutical ingredients. Many drugs have the potentials to be made into orodispersible tablets. They vary from analgesics to neuroleptics and anti-psychotic drugs. However only a small percentage of them are researched on and some have been manufactured and marketed. In this review article, drug candidates suitable for fast dissolving drug delivery and the available marketed products have been listed.
Drug delivery via the oral mucous membrane is considered to be a promising alternative to the oral route. Sublingual route is a useful when rapid onset of action is desired with better patient compliance than orally ingested tablets. In terms of permeability, the sublingual area of the oral cavity (i.e. the floor of the mouth) is more permeable than the buccal (cheek) area, which in turn is more permeable than the palatal (roof of the mouth) area. The portion of drug absorbed through the sublingual blood vessels bypasses the hepatic first-pass metabolic processes giving acceptable bioavailability. Various techniques can be used to formulate sublingual tablets. New sublingual technologies address many pharmaceutical and patient needs, ranging from enhanced life-cycle management to convenient dosing for paediatric, geriatric, and psychiatric patients with dysphagia. This review highlights the different sublingual dosage forms, factors affecting the sublingual absorption, advantages, various in vitro and in vivo evaluation parameters and commercially available sublingual dosage forms.
Drug delivery via sublingual mucous membrane is considered to be a promising alternative to the oral route. This route is useful when rapid onset of action is desired as in the case of antiemetics such as ondansetron. In terms of permeability, the sublingual area of the oral cavity is more permeable than cheek and palatal areas of mouth. The drug absorbed via sublingual blood vessels bypasses the hepatic first-pass metabolic processes giving acceptable bioavailability with low doses and hence decreases the side effects. Sublingual drug delivery system is convenient for paediatric, geriatric, and psychiatric patients with dysphagia. This review highlights the different sublingual dosage forms, advantages, factors affecting sublingual absorption, pharmacology of ondasetron, methods of preparation and various in vitro and in vivo evaluation parameters of sublingual tablet of ondansetron.