ABSORPTION OF DRUG THROUGH NON PER ORAL ROUTES : 1 ABSORPTION OF DRUG THROUGH NON PER ORAL ROUTES BY:
I M.PHARM BUCCAL / SUBLINGUAL ADMINISTRATION : 2 BUCCAL / SUBLINGUAL ADMINISTRATION The two sites for oral mucosal delivery of drugs are:
1.Sublingual route: the drug is placed under the tongue and allowed to dissolve.
2.Buccal route: The medicament is placed between the cheek and the gum.
The barrier to drug absorption from these routes is the epithelium of oral mucosa . Advantages : 3 Advantages 1.Rapid absorption and higher blood levels due to high vascularization of the region and therefore particularly useful for administration of antianginal drugs.
2.No-first pass hepatic metabolism .
3.No degradation of drugs such as encounters in the gastrointestinal tract (GIT) Slide 4: 4 4.Presence of saliva facilitates both drug dissolution and its subsequent permeation by keeping the oral mucosa moist. Factors affecting oral mucosal delivery : 5 Factors affecting oral mucosal delivery 1.Lipophilicity of drug: slightly higher lipid solubility than that required for GI absorption is necessary for passive permeation.
2.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 . Slide 6: 6 3.pHof the saliva: usually around 6,the buccal pH favors absorption of drugs which remain unionized.
4.Binding to oral mucosa: systemic availability of drugs that bind to oral mucosa is poor.
5.Thickness of oral epithelium: sublingual absorption is faster than buccal since epithelium of former region is thinner and immersed in a large volume of saliva. Slide 7: 7 Examples of drug administered by oral mucosal route includes antianginal like nitrites and nitrates ,anti hypertensives like nifedipine, analgesics like morphine and bronchodilators like fenoterol.Certain steroids like estradiol and peptides like oxytocin can also be administered. RECTAL ADMINISTRATION: : 8 RECTAL ADMINISTRATION: Important route for children and old patients usually administered as solutions or suppositories.
The pH of rectal fluids (around 8) also influences drug absorption according to pH partition hypothesis .
Eg:- Aspirin, Paracetamol , Theophylline ,few Barbiturates. TOPICAL ADMINISTRATION : 9 TOPICAL ADMINISTRATION When topically applied drugs are meant to exert their effects systemically, the mode of administration is called as percutaneous or transdermal delivery. Factors influencing passive percutaneous absorption of drugs: : 10 Factors influencing passive percutaneous absorption of drugs: 1.Thickness of stratum corneum
2.Presences of hair follicles
4.Hydration of skin
5.Age: Slide 11: 11 6.Exposure to chemicals
7.Vehicle or base:
9.chronic use of certain drugs:
Eg:- include nitroglycerine ,Lidocaine, Estradiol, Testosterone . INTRAMUSCULAR ADMINISTARTION : 12 INTRAMUSCULAR ADMINISTARTION Absorption of drugs from i.m sites is relatively rapid but much slower in comparison to i.v injections.
1.Vascularity of the injection site:
2.Lipid solubility and ionization of drug:
3.Molecular size of the drug:
4.Volume of injection and drug concentration;
5.pH, composition and viscosity of injection based vehicle. Slide 13: 13 SUBCUTANEOUS ADMINISTARTION : 14 SUBCUTANEOUS ADMINISTARTION Generally absorption of drugs from a s.c is slower than from i.m sites due to poor perfusion , but this fact is of particular importance for administration of drugs for which a rapid response is not desired and for drugs that degrade when taken orally e.g insulin and sodium heparin Slide 15: 15 The rate of absorption of a drug from s.c site can be increased in two ways :
1.Enhancing blood flow to the injection site:
2.increasing the drug tissue contact area:
Absorption can be slowed down by causing vasoconstriction through local cooling or co-injection of a vasoconstrictor like adrenaline or by immobilization of the limb. PULMONARY ADMINISTRATION: : 16 PULMONARY ADMINISTRATION: All drugs intended for systemic effects can be administered by inhalation since the large surface area of the alveoli , high permeability of the alveolar epithelium , and rich perfusion permit extremely rapid absorption just like exchange of gases between the blood and inspired air. Pulmonary : 17 Pulmonary Slide 18: 18 However, this route has been limited for administering drugs that affect pulmonary system such as bronchodilators (salbutamol) ,anti inflammatory steroids, (beclomethasone), lipid soluble drugs are rapidly absorbed by passive diffusions, and polar drugs by polar transport.the drugs are generally administered by inhalation either as gases or aerosols . INTRANASAL ADMINISTRATION : 19 INTRANASAL ADMINISTRATION The nasal route is becoming increasingly popular for systemic delivery especially of some peptide and protein drugs.
Drug absorption from nasal mucosa is rapid because of its rich vasculature or / and high permeability.
There are two mechanisms for drug transport across the nasal mucosa have been suggested:-
A faster rate that is dependent upon drug lipophilicity , and a slower rate that is dependent upon drug molecular weight. Slide 20: 20 Others factors that may influence nasal permeation of drugs include pH of nasal secretions(5.5 to 6.5) and its visocity ,and pathological conditions such as common cold and rhinitis.
Drugs known to influence the cleansing function of nasal cilia should not be administered by this route. INTRAOCULAR ADMINISTRATION : 21 INTRAOCULAR ADMINISTRATION Topical application of drugs to the eyes is mainly meant for local effects such as mydriasis, miosis, anesthesia or treatment of infections, glaucoma,etc.
The barrier to intraocular penetration of drugs is the cornea which posses both hydrophilic and lipophilic characteristics.thus for optimum intraocular permeation ,drugs should posses biphasic solubility Slide 22: 22 Sometimes systemic absorption of a drug with low therapeutic index such as timolol
may percipate undesirable toxic effects.
Systemic entry of drugs may occur by way of absorption into lacrimal duct which drains lacrimal fluid into the nasal cavity and finally into the gastrointestinal tract. Slide 23: 23 This can be prevented by simple eyelid closure or nasolacrimal occlusion by pressing finger tip to the inside corner of the eye after drug distillation. VAGINAL ADMINISTRATION : 24 VAGINAL ADMINISTRATION Drugs meant for intravaginal application are generally intended to act locally in the treatment of bacteria or fungal infections or prevent conception.
The route is now used for systemic delivery of contraceptives and other steroids. Factors that may influence drug absorption from intravaginal site include pHof lumen fluids (4 to 5),vaginal secretions and the micro organisms present in the vaginal lumen which may metabolize the drug. Summary of mechanisms and drug absorbed from various noninvasive routes: : 25 Summary of mechanisms and drug absorbed from various noninvasive routes: Slide 26: 26 Slide 27: 27 Slide 28: 28 THANK YOU