Antidiabetic Buccal Dosage Form

7/31/2019 Antidiabetic Buccal Dosage Form

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1. IntroductionBy, Vikram Viswajit Mishra,

M.Pharma

Jeypore College of Pharmacy

E-mail id [email protected]

The effect of new formulations can be enhanced by the development of newer release

systems. The main controlled drug delivery systems currently available include matrices,

pellets, floating systems, liposomes, microemulsions, liquid crystals, solid dispersions,

nanosuspensions, transdermal systems, cyclodextrin inclusion complexes, osmotic pumps and

bioadhesive systems. The potential use for mucoadhesive systems as drug carriers lies in its

prolongation of the residence time at the absorption site, allowing intensified contact with the

epithelial barrier. When adhesion is restricted to the mucosal membrane it is called as

mucoadhesion. Mucous membrane is the main administration site for bioadhesive systems.

Mucous membranes of human organism are relatively permeable and allow fast drug

absorption. They are characterized by an epithelial layer whose surface is covered by mucus.

This approach to confer bioadhesion properties has been widely applied in the development

of a number of drug delivery systems.

[1-2]

The Mucosal Buccal Delivery has brought about a great change in the pharmaceutical

arena. It produces a sustained release of drug over a prolonged time, thereby reducing

frequent dosing. The area is well suited for a retentive device and appears to be acceptable to

the patient. With the right dosage form design and formulation, the permeability and the local

environment of the mucosa can be controlled and manipulated in order to accommodate drug

permeation. Buccal drug delivery is a promising area for continued research with the aim of

systemic delivery of orally inefficient drugs as well as a feasible and attractive alternative for

non-invasive delivery of potent peptide and protein drug molecules.[3- 4]

1.1 Diabetes

Diabetes is a group of metabolic diseases in which a person has high blood sugar, either

because the body does not produce enough insulin, or because cells do not respond to the

insulin that is produced. This high blood sugar produces the classical symptoms of polyuria(frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger).


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Diabetes is a condition in which the quantity of glucose in the blood is raised called

hyperglycemia. This happens when there is low or no insulin production or improper use of

insulin.

Types of Diabetes

There are two major types of diabetes. They are as follows:

1. Type 1 DM: It results from the body's failure to produce insulin, and presentlyrequires the person to inject insulin. (Also referred to as insulin-dependent diabetes

mellitus (IDDM) or "juvenile" diabetes). Type 1 diabetes can occur in an older

individual due to destruction of the pancreas by alcohol, disease, or removal by

surgery.

2. Type 2 DM: It results from insulin resistance, a condition in which cells fail to useinsulin properly, sometimes combined with an absolute insulin deficiency. (Formerly

referred to as noninsulin-dependent diabetes mellitus (NIDDM) or "adult-onset"

diabetes).

Epidemiology

Globally, as of 2010, an estimated 285 million people had diabetes, with type 2 making up

about 90% of the cases. Its incidence is increasing rapidly, and by 2030, this number is

estimated to almost double. Diabetes mellitus occurs throughout the world, but is more

common (especially type 2) in the more developed countries. The greatest increase in

prevalence is, however, expected to occur in Asia and Africa, where most patients will

probably be found by 2030. The increase in incidence in developing countries follows the

trend of urbanization and lifestyle changes, perhaps most importantly a "Western-style" diet.

This has suggested an environmental (i.e., dietary) effect, but there is little understanding of

the mechanism(s) at present, though there is much speculation, some of it most compellingly

presented. India has more diabetics than any other country in the world, according to the

International Diabetes Foundation, although more recent data suggest that China has even

more. The disease affects more than 50 million Indians - 7.1% of the nation's adults - and

kills about 1 million Indians a year. The average age on onset is 42.5 years. The high


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incidence is attributed to a combination of genetic susceptibility plus adoption of a high-

calorie, low-activity lifestyle by India's growing middle class.[6-7]

Pathology of Diabetes

Diabetes (Hyperglycemia), which is defined as fasting plasma glucose above 126 mg/dl &

oral glucose tolerance test (OGTT) above 200 mg/dl

Pre-Diabetes is defined as impaired fasting glucose (IFG) of 100-125 mg/dl & impaired

glucose tolerance (IGT) of 140-199 mg/dl

Acute Complications of Uncontrolled Diabetes (all directly caused by hyperglycemia)

--Polyuria due to excess fluid intake and glucose-induced osmotic diuresis --Weight loss due to calories lost as glucosuria, leaving a negative calorie balance --Poor wound healing, gingivitis, blurred vision

Chronic Complications of Uncontrolled Diabetes

Chronic complications may be due to mitochondrial superoxide overproduction in response to

hyperglycemia.

Macro vascular Atherosclerosis: diabetics have a high incidence of coronary, cerebral, and

peripheral artery diseases. Caused by dyslipidemias including elevated LDL and triglycerides,

low HDL, and reduced fibrinolysis activity. Management includes foot care.

Micro vascular Diseases of Diabetes

1. Diabetic Retinopathy has many manifestations, including micro aneurysms, microhemorrhages, proliferative vessel changes, and vitreous bleeds (cause blindness). Diabetic

retinopathy is caused by basement membrane deterioration and ischemia.

2. Nephropathy progresses from micro albuminuria to proteinuria to uremia to ESRD.

Nephropathy is caused by hyper filtration, increased glomerular pressure, and BM thickening.

End stage Complications of Uncontrolled Diabetes


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Sign and symptoms

In both types of diabetes, signs and symptoms are more likely to be similar as the blood sugar

is high, either due to less or no production of insulin, or insulin resistance. In any case, if

there is inadequate glucose in the cells, it is identifiable through certain signs and symptoms.

These symptoms are quickly relieved once the Diabetes is treated and also reduce the chances

of developing serious health problems .

DiabetesType1:

In type 1, the pancreas stop producing insulin due to autoimmune response or possibly viral

attack on pancreas. In absence of insulin, body cells dont get the required glucose forproducing ATP (Adenosin Triphosphate) units which results into primary symptom in the

form of nausea and vomiting. In later stage, which leads to ketoacidosis, the body starts

breaking down the muscle tissue and fat for producing energy hence, causing fast weight loss.

Dehydration is also usually observed due to electrolyte disturbance. In advanced stages, coma

and death is witnessed .

Diabetes Type 2:

Increased fatigue: Due to inefficiency of the cell to metabolize glucose, reserve fat ofbody is metabolized to gain energy. When fat is broken down in the body, it uses

more energy as compared to glucose, hence body goes in negative calorie effect,

which results in fatigue.

Polydipsia: As the concentration of glucose increases in the blood, brain receivessignal for diluting it and, in its counteraction we feel thirsty.
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Polyuria: Increase in urine production is due to excess glucose present in body. Bodygets rid of the extra sugar in the blood by excreting it through urine. This leads to

dehydration because along with the sugar, a large amount of water is excreted out of

the body.

Polyphagia : The hormone insulin is also responsible for stimulating hunger. In orderto cope up with high sugar levels in blood, body produces insulin which leads to

increased hunger.

Blurry vision: Hyperosmolar hyperglycemia nonketotic syndrome is the conditionwhen body fluid is pulled out of tissues including lenses of the eye, which affects its

ability to focus, resulting blurry vision.

Poor wound healing : High blood sugar resists the flourishing of WBC, (white bloodcell) which are responsible for body immune system. When these cells do not function

accordingly, wound healing is not at good pace. Secondly, long standing diabetes

leads to thickening of blood vessels which affect proper circulation of blood in

different body parts.[8]

Treatment

The major goal in treating diabetes is to minimize any elevation of blood sugar (glucose)without causing abnormally low levels of blood sugar. Type 1 diabetes is treated with insulin,

exercise, and a diabetic diet. Type 2 diabetes is treated first with weight reduction, a diabetic

diet, and exercise. When these measures fail to control the elevated blood sugars, oral

medications are used. If oral medications are still insufficient, treatment with insulin is

considered. Adherence to a diabetic diet is an important aspect of controlling elevated blood

sugar in patients with diabetes.Weight reduction and exercise increase the body's sensitivity

to insulin, thus helping to control blood sugar elevations.

Testosterone replacement therapy may improve glucose tolerance and insulin sensitivity in

diabetic hypogonadal men. The mechanisms by which testosterone decreases insulin

resistance is under study. Moreover testosterone may have a protective effect on pancreatic

beta cells, which is possibly exerted by androgen-receptor-mediated mechanisms and

influence of inflammatory cytokines. Recentlyit has been suggested that a type ofgastric

bypass surgery may normalize blood glucose levels in 80-100% of severely obese patients

with diabetes.. This approach may become a treatment for some people with type 2 diabetes,

but has not yet been studied in prospective clinical trials.[94]

This surgery may have the
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additional benefit of reducing the death rate from all causes by up to 40% in severely obese

people.[95]

A small number of normal to moderately obese patients with type 2 diabetes have

successfully undergone similar operations.

MODY is another classification of diabetes and it can be treated by early lifesyle

management and medical management. it has to be treated in the early stage, so as to provide

a good health.[9]

1.2 Mucoadhesive Buccal Drug Delivery

Buccal drug delivery is a promising area for continued research and attractive alternative for

non-invasive delivery of potent peptide and protein drug molecules. Buccal administration of

drugs provides a convenient route of administration for both systemic and local drug actions.

The need for safe and effective buccal permeation absorption enhancers is a crucial

component for a prospective future in the area of buccal drug delivery. Buccal nitroglycerin,

can use for acute therapy for an animal attack as well as for chronic prophylaxis Novel liquid

aerosol formulation of insulin Development of suitable delivery devices, permeation

enhancement, and Buccal delivery of drugs that undergo a first-pass effect, such as

cardiovascular drugs, analgesics, and peptides Research yield some successes Promote

further research; more companies Rest depend on delivery technology.[10]

Buccal Route of Drug Absorption

There are two permeation pathways for passive drug transport across the oral mucosa:

paracellular and transcellular routes. Permeants can use these two routes simultaneously, but

one route is usually preferred over the other depending on the physicochemical properties of

the diffusant. Since the intercellular spaces and cytoplasm are hydrophilic in character,

lipophilic compounds would have low solubility in this environment. The cell membrane,

however, is rather lipophilic in nature and hydrophilic solutes will have difficulty permeating

through the cell membrane due to a low partition coefficient. Therefore, the intercellular

spaces pose as the major barrier to permeation of lipophilic compounds and the cell

membrane acts as the major transport barrier for hydrophilic compounds. Since the oral

epithelium is stratified, solute permeation may involve a combination of these two routes.

The route that predominates, however, is generally the one that provides the least amount of

hindrance to passage.
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Buccal mucosa as a site for Drug Delivery

There are three different categories of drug delivery within the oral cavity (i.e.,

Sublingual, buccal, and local drug delivery). Selecting one over another is mainly based on

anatomical and permeability differences that exist among the various oral mucosal sites. The

sublingual mucosa is relatively permeable, giving rapid absorption and acceptable

bioavailability of many drugs, and is convenient, accessible, and generally well accepted .The

sublingual route is by far the most widely studied of these routes. Sublingual dosage forms

are of two different designs, those composed of rapidly disintegrating tablets, and those

consisting of soft gelatin capsules filled with liquid drug. Such systems create a very high

drug concentration in the sublingual region before they are systemically absorbed across the

mucosa. Local delivery to tissues of the oral cavity has a number of applications, including

the treatment of toothaches, periodontal disease, bacterial and fungal infections, and dental

stomatitis, and in facilitating tooth movement with prostaglandins. First difference being in

the permeability characteristics of the region, where the buccal mucosa is less permeable and

is thus not able to give a rapid onset of absorption (i.e., more suitable for a sustained release

formulation). Second being that, the buccal mucosa has an expanse of smooth muscle andrelatively immobile mucosa which makes it a more desirable region for retentive systems

used for oral transmucosal drug delivery. Thus the buccal mucosa is more fitted for sustained

delivery applications, delivery of less permeable molecules, and perhaps peptide drugs.

1.3 Advantages of Mucosal Buccal Drug Delivery

1. Bypass of the gastrointestinal tract and hepatic portal system, increasing the bioavailability

of orally administered drugs that otherwise undergo hepatic first-pass metabolism. In addition

the drug is protected from degradation due to pH and digestive enzymes of the middle

gastrointestinal tract

2. Improved patient compliance due to the elimination of associated pain with injections;

administration of drugs in unconscious or incapacitated patients; convenience of

administration as compared to injections or oral medications.

3. Sustained drug delivery.


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4. A relatively rapid onset of action can be achieved relative to the oral route, and the

formulation can be removed if therapy is required to be discontinued.

5. Increased ease of drug administration.

6. Though less permeable than the sublingual area, the buccal mucosa is well vascularized,

and drugs can be rapidly absorbed into the venous system underneath the oral mucosa.

7. In comparison to TDDS, mucosal surfaces do not have a stratum corneum. Thus, the major

barrier layer to transdermal drug delivery is not a factor in transmucosal routes of

administration. Hence transmucosal systems exhibit a faster initiation and decline of delivery

than do transdermal patches.

8. Transmucosal delivery occurs is less variable between patients, resulting in lower

intersubject variability as compared to transdermal patches.[11-14]

1.4 Limitations of Mucosal Buccal Drug Delivery

1. For local action the rapid elimination of drugs due to the flushing action of saliva or the

ingestion of foods stuffs may lead to the requirement for frequent dosing. Depending on

whether local or systemic action is required the challenges faced while delivering drug via

buccal drug delivery can be enumerated as follows.

2. The non-uniform distribution of drugs within saliva on release from a solid or semisolid

delivery system could mean that some areas of the oral cavity may not receive effective

levels.

3. For both local and systemic action, patient acceptability in terms of taste, irritancy and

mouth feel is an issue.[11-14]


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1.5 Overview of the Oral Mucosa

Structure

The oral mucosa is composed of outermost layer of stratified epithelium.Below lies a

basement membrane, a lamina prairie followed by the submucosa as the innermost layer. The

epithelium is similar to stratified squamous epithelia found in the rest of the body in that it

has a mitotically active basal cell layer, advancing through a number of differentiating

intermediate layers to the superficial layers, where cells are shed from the surface of the

epithelium18. The epithelium of the buccal mucosa is about 40-50 cell layers thick, while that

of the sublingual epithelium contains somewhat fewer. The epithelial cells increase in size

and become flatter as they travel from the basal layers to the superficial layers. The turnover

time for the buccal epithelium.It has been estimated at 5-6 days, and this is probably

representative of the oral mucosa as a whole. The oral mucosal thickness varies depending on

the site: the buccal mucosa measures at 500-800 m, while the mucosal thickness of the hard

and soft palates, the floor of the mouth, the ventral tongue, and the gingival measure at about

100-200 m.[15]

Fig 1.2. Section of buccal mucosal layer


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Permeability

The oral mucosa in general is a somewhat leaky epithelial intermediate between that of the

epidermis and intestinal mucosa. It is estimated that the permeability of the buccal mucosa is

4-4000 times greater than that of the skin . As indicative by the wide range in this reported

value, there are considerable differences in permeability between different regions of the oral

cavity because of the diverse structures and functions of the different oral mucosae. In

general, the permeabilities of the oral mucosae decrease in the order of sublingual greaterthan

buccal, and buccal greater than palatal. This rank order is based on the relative thickness and

degree of keratinization of these tissues, with the sublingual mucosa being relatively thin and

non-keratinized, the buccal thicker and non-keratinized, and the palatal intermediate in

thickness but keratinized. The MCGs of keratinized epithelium are composed of lamellar

lipid stacks, whereas the non-keratinized epithelium contains MCGs that are non-lamellar.

The MCG lipids of keratinized epithelia include sphingomyelin, glucosylceramides,

ceramides, and other nonpolar lipids, however for non-keratinized epithelia, the major MCG

lipid components are cholesterol esters, cholesterol, and glycosphingolipids Aside from the

MCGs, the basement membrane may present some resistance to permeation as well,however

the outer epithelium is still considered to be the rate limiting step to mucosal penetration. The

structure of the basement membrane is not dense enough to exclude even relatively large

molecules.[16]

Environment

The cells of the oral epithelia are surrounded by an intercellular ground substance, mucus, theprinciple components of which are complexes made up of proteins and carbohydrates. These

complexes may be free of association or some maybe attached to certain regions on the cell

surfaces. This matrix may actually play a role in cell-cell adhesion, as well as acting as a

lubricant, allowing cells to move relative to one another. Along the same lines, the mucus is

also believed to play a role in bio adhesion of mucoadhesive drug delivery systems. In

stratified squamous epithelia found elsewhere in the body, mucus is synthesized by

specialized mucus secreting cells like the goblet cells, however in the oral mucosa, mucus is

secreted by the major and minor salivary glands as part of saliva . Up to 70% of the total


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mucin found in saliva is contributed by the minor salivary glands . At physiological pH the

mucus network carries a negative charge (due to the sialic acid and sulfate residues) which

may play a role inmucoadhesion. At this pH mucus can form a strongly cohesive gel structure

that will bind to the epithelial cell surface as a gelatinous layer.

1.6 Mechanism of Mucoadhesion

The mechanism of adhesion of certain macromolecules to the surface of a mucous tissue is

not well understood yet. The mucoadhesive must spread over the substrate to initiate close

contact and increase surface contact, promoting the diffusion of its chains within the mucus.

Attraction and repulsion forces arise and, for a mucoadhesive to be successful, the attraction

forces must dominate. Each step can be facilitated by the nature of the dosage form and how

it is administered. For example, a partially hydrated polymer can be adsorbed by the substrate

because of the attraction by the surface water. Thus, the mechanism of mucoadhesion is

generally divided in two steps, the contact stage and the consolidation stage (Figure1.3). The

first stage is characterized by Mucoadhesive drug delivery systems 3 the contact between the

mucoadhesive and the mucous membrane, with spreading and swelling of the formulation,

initiating its deep contact with the mucus layer .In some cases, such as for ocular or vaginal

formulations, the delivery system is mechanically attached over the membrane. In other

cases, the deposition is promoted by the aerodynamics of the organ to which the system is

administered, such as for the nasal route. On the other hand, in the gastrointestinal tract direct

formulation attachment over the mucous membrane is not feasible. Peristaltic motions can

contribute to this contact, but there is little evidence in the literature showing appropriate

adhesion. Additionally, an undesirable adhesion in the esophagus can occur. In these cases,

mucoadhesion can be explained by peristalsis, the motion of organic fluids in the organ

cavity, or by Brownian motion. If the particle approaches the mucous surface, it will come

into contact with repulsive forces (osmotic pressure, electrostatic repulsion, etc.) and

attractive forces (van der Waals forces and electrostatic attraction). Therefore, the particle

must overcome this repulsive barrier. In the consolidation step (Figure 1.3), the

mucoadhesive materials are activated by the presence of moisture. Moisture plasticizes the

system, allowing the mucoadhesive molecules to break free and to link up by weak van der

Waals and hydrogen bonds. Essentially, there are two theories explaining the consolidation

step: the diffusion theory and the dehydration theory. According to diffusion theory, the

mucoadhesive molecules and the glycoproteins of the mucus mutually interact by means of


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interpenetration of their chains and the building of secondary bonds .For this to take place the

mucoadhesive device has features favoring both chemical and mechanical interactions. For

example, molecules with hydrogen bonds building groups (OH, COOH), with an anionic

surface charge, high molecular weight, flexible chains and surface-active properties, which

induct its spread throughout the mucus layer, can present mucoadhesive properties.[17]

Fig 1.3 The two steps of mucoadhesive process

1.7 Mucoadhesive Theories

There are six classical theories adapted from studies on the performance of several materials

and polymer-polymer adhesion which explain the phenomenon

Electronic theory

Electronic theory is based on the fact that both mucoadhesive and biological materials

possess opposing electrical charges. Thus, when both materials come into contact, they

transfer electrons leading to the building of a double electronic layer at the interface, where

the attractive forces within this electronic double layer determines the mucoadhesive strength.

Adsorption theory

According to the adsorption theory, the mucoadhesive device adheres to the mucus by

secondary chemical interactions, such as in van der Waals and hydrogen bonds, electrostatic


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attraction or hydrophobic interactions For example, hydrogen bonds are the prevalent

interfacial forces in polymers containing carboxyl groups .Such forces have been considered

the most important in the adhesive interaction phenomenon because, although they are

individually weak, a great number of interactions can result in an intense global adhesion

Wetting theory

The wetting theory applies to liquid systems which present affinity to the surface in order to

spread over it. This affinity can be found by using measuring techniques such as the contact

angle. The general rule states that the lower the contact angle then the greater the affinity

(Figure 1.3). The contact angle should be equal or close to zero to provide adequate spread

ability

Fig. 1.4 .Schematic diagram showing influence of contact angle between device and

mucous membrane

Fracture theory

This is perhaps the most-used theory in studies on the mechanical measurement of

mucoadhesion. It analyses the force required to separate two surfaces after adhesion is

established


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Mechanical theory

Mechanical theory considers adhesion to be due to the filling of the irregularities on a rough

surface by a mucoadhesive liquid. Moreover, such roughness increases the interfacial area

available to interactions thereby aiding dissipating energy and can be considered the most

important phenomenon of the process. It is unlikely that the mucoadhesion process is the

same for all cases and therefore it cannot be described by single theory. The mechanisms

governing mucoadhesion are also determined by the intrinsic properties of the formulation

and by the environment in which it is applied. Intrinsic factors of the polymer are related to

its molecular weight, concentration and chain flexibility. For linear polymers, mucoadhesion

increases with molecular weight, but the same relationship does not hold for nonlinear

polymers.[18]

1. 8 Factors Affecting Drug Delivery via Buccal Route

The rate of absorption of hydrophilic compounds is a function of the molecular size. Smaller

molecules (75-100 Da) generally exhibit rapid transport across the mucosa, with permeability

decreasing as molecular size increases. For hydrophilic macromolecules such as peptides,

absorption enhancers have been used to successfully alter the permeability of the buccal

epithelium, causing this route to be more suitable for the delivery of larger molecules

1. 9 Methods to Increase Drug Delivery via Buccal Route

(1) Absorption enhancers:

Absorption enhancers have demonstrated their effectiveness in delivering high molecular

weight compounds, such as peptides, that generally exhibit low buccal absorption rates.[19]


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Table 1.1: List of Permeation Enhancers

Sr. no Permeation Enhancers Sr. no Permeation Enhancers

1 2,3-Lauryl ether 9 Phosphatidylcholine

2 Aprotinin 10 Polyoxyethylene

3 Azone 11 Polysorbate 80

4 Benzalkonium chloride 12 Polyoxyethylene

5 Cetylpyridinium chloride 13 Phosphatidylcholine

6 Cetyltrimethyl ammonium bromide 14 Sodium EDTA

7 Cyclodextrin 15 Sodium glycoholate

8 Dextran sulfate 16 Sodium glycodeoxycholate

(2) Prodrugs:

Hussein et al delivered opioid agonists and antagonists in bitterness prodrug forms and found

that the drug exhibited low bioavailability as prodrug. Nalbuphine and naloxone bitter drugs

when administered to dogs via the buccal mucosa, the caused excess salivation and

swallowing. As a result, the drug exhibited low bioavailability.[20]

(3) pH :

Shojaei et al evaluated permeability of acyclovir at pH ranges of 3.3 to 8.8, and in the

presence of the absorption enhancer, sodium glycocholate. The in vitro permeability of

acyclovir was found to be pH dependent with an increase in flux and permeability coefficient

at both pH extremes (pH 3.3 and 8.8), as compared to the mid-range values (pH 4.1, 5.8, and

7.0).


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(4) Patch design:

Several in vitro studies have been conducted regarding on the type and amount of backing

materials and the drug release profile and it showed that both are interrelated.

Also, the drug release pattern was different between single-layered and multi-layered patches.

1.4 Classifications of buccal bioadhesive dosage forms

1. Buccal Bioadhesive Tablets.

2. Buccal Bioadhesive semisolids

3. Buccal Bioadhesive patch and films

4. Buccal Bioadhesive Powders

1. Buccal bioadhesive tablets

Buccal bioadhesive tablets are dry dosage forms that are to be moistened prior to placing in

contact with buccal mucosa. Double and multilayered tablets are already formulated using

bioadhesive polymers and excipients. The two buccal bioadhesive tablets commercially

available buccoadhcsive tablets in UK are "Bucastem" and Suscard buccaP'.

2. Buccal bioadhesivc semisolid dosage forms

Buccal bioadhesive semisolid dosage forms consists of finally powdered natural or synthetic

polymer dispersed in a polyethylene or in aqueous solution, Example: Arabase.21

3. Buccal bioadhesive patches and films

Buccal bioadhesive patches consists of two ply laminates or multilayered thin film round or

oval as consisting of basically of bioadhesive polymeric layer and impermeable backing layer

to provide unidirectional flow of drug across buccal mucosa. Buccal bioadhesive films arc

formulated by incorporating the drug in alcohol solution of bioadhesive polymer.


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4.Buccal bioadhesive powder dosage forms

Buccal bioadhesive powder dosage forms are a mixture of Bioadhesive polymers and the

drug and are sprayed onto the buccal mucosa the reduction in diastolic B.P after the

administration of buccal tablet and buccal film of Nifedipine.

1.10 Basic Components of Buccal Bioadhesive Drug Delivery

The basic components of buccal bioadhesive drug delivery system are

1. Drug substance2. Bioadhesive polymers3. Backing membrane4. Penetration enhancers5. Adhesives

1. Drug substance:

Before formulating buccoadhcsive drug delivery systems, one has to decide whether the

intended, action is for rapid release/prolonged release and for local/systemic effect The drug

should have following characteristics.[21]

1. The conventional single dose of the drug should be small.

The drugs having biological half-life between 2-8 hours are good candidates for controlled

drug delivery.

2. Tmax of the drug shows wider-fluctuations or higher values when given orally.30

3. The drug absorption should be passive when given orally.

2. Bioadhesive polymers:

The first step in the development of buccoadhcsive dosage forms is the selection and

characterization of appropriate bioadhesive polymers in the formulation." Bioadhesive

polymers play a major role in buccoadhcsive drug delivery systems of drugs. Polymers arc

also used in matrix devices in which the drug is embedded in the polymer matrix, which

controls the duration of release of drugs

An ideal polymer for buccoadhcsive drug delivery systems should have following

Characteristics:


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It should be inert and compatible with the environment The polymer and its degradation products should be non-toxic absorbable from the

Mucous layer.

It should adhere quickly to moist tissue surface and should possess some sitespecificity.

The polymer must not decompose on storage or during the shelf life of the dosageform.

The polymer should be easily available in the market and economical.3. Backing membrane: Backing membrane plays a major role in the attachment of

bioadhesive devices to the mucus membrane. The materials used as backing membrane

should be inert, and impermeable to the drug and penetration enhancer. The commonly used

materials in backing membrane include carbopol, magnesium separate, HPMC, HPC, CMC,

polycarbophil etc.

4. Penetration enhancers: Penetration enhancers arc used in buccoadhcsive formulations to

improve the release of the drug. They aid in the systemic delivery of the drug by allowing the

drug to penetrate more readily into the viable tissues.

5. Bioadhesion: Bioadhesive are the substances that are capable of interacting with the

biological material and being retained on them or holding them together for extended periodof time.Bioadhesive can be used to apply to any mucous or no mucous membranes and it also

increases intimacy and duration of contact of the drug with the absorbing membrane. The

commonly used bioadhesive are sodium alginate, carbomers, polycarbophil, HPMC, HPC,

gelatin etc.


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1.11 LIST OF DRUGS DELIVERED VIA BUCCAL ROUTE.

Table 1.2: List of drugs delivered via buccal route

Sr.No Active Ingredients

1 Acitretin

2 Acyclovir

3 Arecoline

4 Buprenorpine

5 Carbamazepine

6 Cetyl Pyridium Chloride

7 Chitosan

8 Chlorpheniramine Maleate

9 Cyanocobalamine

10 Danazol

11 Denbufylline

12 Diclofenac Sodium

13 Diltiazem Hydrochloride

14 Ergotamine Tartrate

15 Fluride

16 Metronidazole

17 Melatonin

18 Metoprolol

19 Morphine Sulphate

20 Nalbuphine

21 Nicotine

22 Nifedipine

23 Omeprazole

24 Oxytocin

25 Pindolol


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26 Propolis

1.12 Mucoadhesive Buccal Tablet

Mucoadhesive Buccal tablets comprising hydrogels can adhere to the buccal mucosa. They

are similar to conventional tablets and are prepared by wet granulation, dry granulation, or

direct compression processes. Drug is released upon the hydration and adhesion of the

device. Buccal tablets should be fabricated and optimized for swelling behavior and drug

release to ensure a prolonged period of bioadhesion and sustained or controlled release.

Generally, the tablets are formulated with flat punches with dimensions less than 10 mm in

diameter and 2 mm thick to aid in establishing intimate contact with buccal mucosa and

reduce their interference with normal activities. In addition to mucoadhesive components,

most of the tablets contained water-soluble excipients such as high-molecular-weight

polyethylene glycols and mannitol.[22-24]

Documents

Antidiabetic Buccal Dosage Form