Formulation of Buccal Drug Delivery System

Buccal drug delivery system is an advanced type of drug delivery system where the drug is passed into the specific site without must wastage ! It is a novel drug delivery system where the medicament avoids 1st pass metabolism, which increases its bio availability !
* Types include matrix type and reservoir type in which 2nd type is more advanced and shows quick absorption of the drug .
* I have mentioned it's advantages and disadvantages.
* Factors effecting the drug delivery system
*Formulation of the BDDS
* Evaluation parameters

1. B U C C AL DRUG DELIVERY SYSTEM - K . H I M A N I 3 R D P H A R M - D S V C P 2 1 P 9 1 T 1 4

2. B U C C A L DRUG DELIVERY SYSTEM Delivery of drug throw buccal mucosa of oral cavity is known as Buccal drug delivery. Buccal administration involves placement of the drug between the gums and the cheek. Medications available in the form of tablets, films, or sprays. o Size: 1–3 cm2 o Daily dose: 25 mg or less. o Maximal duration of buccal delivery

3. S t r u cture of o r a l m u c o s a

4. R o u t e of D r u g A d m i nistration

5. A d v a n t a g e s 1. Relatively large surface area for administra t i o n 2. Systemic absorption is rapid 3. Rich blood Supply 4. Selective use of therapeutic agents like peptides, proteins, hormones and ionized species can be achieved. 5. Robus t 6. Prolonged residence time of drug 7. Administration of drugs with short half life and flexibility in shifting the position in buccal cavity.

6. D i s a d v a n t a g e s 1. Only drugs with small dose requirement can be administered. 2. By mistake tablet can be swallowed. 3. Eating and drinking may be restricted. 4. Drugs which are unstable at buccal pH cannot be administered. 5. Drugs which irritates mucosa or have bitter or unpleasant taste cannot be administered. 6. Saliva may take some drug into gut. 7. Drugs absorbed by passive diffusion can be administered by this route.

7. F a c t o rs I n f l uencing Drug A b s o rption f r o m t h e o r a l c a v i t y B i o l o g i c a l f a c tors Permeability Blood flow (2.4 ml/min/cm) Thickness (500-800μm) pH of environment Saliva flow rate D r u g F a c t o r s Drug Solubility Partition coefficient Ionization Molecular size F o r m u l ation f a c tors Size and shape Properties of excipient Retentive property Texture Release characteris tics

8. L i s t o f d r u g s g i v e n b y B D D S Metronidazole Acyclovir Melatonin Morphine sulphate Carbamazepine Nalbuphine Cetyl Pyridinium chloride Nicotine Chlorhexidine diacetate Nifedipine Omeprazole

9. S t r u cture and d e s i g n o f B u c c a l d o s a g e f o r m s I t i s mainly o f 2 type s 1 . M a t r i x t y p e 2 . R e s e r v o i r t y p e Matrix type: The buccal patch designed in a matrix configuration contains drug, adhesive, and additives mixed together. Reserviour type: The buccal patch designed in a reservoir system contains a cavity for the drug and additives separate from the adhesive. An impermeable backing is applied to control the direction of drug delivery; to reduce patch deformation and disintegration while in the mouth; and to prevent drug loss.

10. M a t r i x t y p e R e s e r voir type

11. Types o f b u c c a l m u c o adhesive p o l y m e r s ✔️ Buccal mucoadhesive dosage forms can be categorized into three types based on their geometry: Type 1: M u l t i d i r e c t i o n a l 🔺 It is a single layer device with multidirectional drug release. This type of dosage form suffers from significant drug loss due to swallowing . Type II: B i l a y e r e d 🔺 It is a device in which an impermeable backing layer is superimposed on top of the drug loaded bioadhesive layer, creating a double-layered device and preventing drug loss from the top surface into the oral cavity Type III: U n i d i r e c t i o n a l 🔺 It is a unidirectional drug release device, from which drug loss is minimal, since the drug is released only from the side adjacent to the buccal mucosa. This can be achieved by coating every face of the dosage form, except the one that is in contact with the buccal mucosa

12. 🔺 To achieve unidirectional release of drug, water impermeable materials 1 . Ethyl cellulose, 2 . Hydrogenated castor oil. Either by compression or by spray coating to coat every face of the tablet except the one that is in contact with the buccal mucosa

13. 2 . B I O A D H E S I V E P O L Y M E R S F o r m ulation c o n s i d e r a t i o n s f o r B D D S 1.DRUG SUBSTANCE 3 .BAC KING MEM BRANE 4 . A D H E S I V E S

14. 1. Drug Substance : - Before formulating buccoadhesive drug delivery systems, one has to decide whether the intended, action is for rapid release/prolonged release and for local/systemic effect. The s e l e c tion of suitable drug for the design of buccoadhesive drug delivery systems should be based on pharmacokinetic properties. The drug should have following characteristics: The conventional single dose of the drug should be small. T h e drugs having biological half-life between 2-8 hours are good candidates for controlled drug delivery.

15. 3. Through oral route drug may exhibit first pass effect or presystemic drug eliminatio n . 4.The drug absorption should be passive when given orally. 2 . B i o adhesive polymer : - which adheres to the mucin/epithelial surface is effective and lead to s i g nificant improvement in the oral drug delivery. An ideal polymer for buccoadhesive drug d e l i v ery systems should have following characteristics. It should be inert and compatible with the environment and biological membrane. The polymer and its degradation products should be non-toxic absorbable from the m u c ous laye r . I t should possess some site specificity

16. 4 . It should adhere quickly to moist tissue surface and should possess some site specificity. 5 . The polymer must not decompose on storage or during the shelf life of the dosage form . 6 . The polymer should be easily available in the market and economical. 7 . It should allow easy incorporation of drug in to the formulation. E x : N a t ura l p olymers: Gelatin, sodium alginate. S y n t hetic and semisynthetic polymers: PVA, PEG, HPMC, PVP, carbomers etc.

17. 3 . B a c k i ng 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. Such impermeable membrane on buccal bioadhesive patches prevents the drug loss and offers better patient compliance. The commonly used materials in backing membrane include carbopol, magnesium stearate, HPMC, HPC, CMC, polycarbophil etc.

18. 4. Penetration Enhancers : - A b s o r ption enhancers have demonstrated their effectiveness in delivering high molecular weight compounds, such as peptides, that generally exhibit low buccal absorption rates. These may act by a v a r i o u s mechanisms, such as increasing the fluidity of the cell membrane, extracting inters/intracellular lipids, altering cellular proteins or altering surface mucin . Ex : sodium lauryl sulphate, CPC, polysorbate 80, laureth-9, sodium fusidate, polmitoyl carnitine, azone, sodium glycocholate, dimethyl formamide, fatty acids and bile salt

19. 4 . B ioadhesives : - B i oadhesives are the substances that are capable of interacting with the biological material and being retained on them holding them together for extended period of time. Bioadhesive can be used to apply to any mucous or nonmucous membranes and it also increases intimacy and duration of contact of the drug with the absorbing membrane. E x : sodium alginate, carbomers, polycarbophil, HPMC, HPC, gelatin etc. The ideal properties of bioadhesive are as follows: It should not produce any residue on mucosa layer. It should be inert and compatible with biological environment. It should adhere to the mucus membrane aggressively. It should preferably form a strong noncovalent bond with mucin/epithelial cell surface

20. E v a luation o f t h e B u c c a l d o s a g e f o r m s

21. Viscosity studies • The rheological studies were carried out using Brookfield programmable DVIII + model pro II type (USA). Spreadability • For the determination of spreadabilty, excess of sample was applied in between two glass slides and was compressed to uniform thickness by placing 1000g weight for 5min. Weight (50g) was added to the upper glass slide. The time in which the upper glass slide moves over to the lower plate was taken as measure of spreadability (S) . S w elling Index • The films were weighed individually and placed on the surface of an agar plate kept in an incubator maintained at 37±0.2°c and the samples were allowed to swell. • An increase in the weight of the film was noted in regular intervals of time and the weight was calculated.

22. The percent swelling, %S was calculated using the following equation: Percent Swelling (%S) = % Swelling index = [(W2-W1)/W1] x100 Where, W 2 = the weight of the swollen film after time W 1 = the initial film weight at zero time. Residence time: • Take a slide, stick a mucosa on it with gum. • P l ace our dosage form on it with few droplets of PBS with p.H (6.8), allow it to stick on it. • Now make it inclined & at constant rate add PBS 6.8 drop wise on it without moving the slide. • Note the time till dosage form detaches from mucosa