When eye surface is covered with the HYPOTONIC SOLUTION, the permeability of the epithelium is increased considerably and water flows in to the cornea, the corneal tissue swell, increasing the pressure on the nerves and causing anaesthetizing action on the cornea.
In case of HYPERTONIC SOLUTIONS water flows from the aqueous layer through the cornea to the eye surface.
Racial differences in oral drug bioavailability are known to exist and may be due to environmental, dietary or genetic differences.
These differences are becoming increasingly important in therapeutics due to, increasingly international nature of drug development and use and also the multi-racial nature of population of many countries.
The most profound differences are found in metabolic processes.
Bioavailability testing is a mean of predicting the clinical efficacy of a drug in a given dosage form is a direct evidence of the efficiency with which a dosage form performs its intended therapeutic function.
Bioavailability studies are also carried out to compare the availability of a drug substance from different dosage forms, or from the same dosage form produced by different manufacturers.
Ophthalmologist prefers topical application to the eye for treating eye diseases. Due to the toxicity of some drugs such as anticholinesterase inhibitor & cholinergic drugs they cannot be used systemically.
Relatively poor ocular bioavailability(2-10 % of the applied dose) is due to:
Narrow pH range, rapid drainage, facilitated elimination by blinking, induced tearing from mechanical or chemical stimulation & small surface area.
The particle size of suspended drugs is below 10 micrometer to prevent abrasion of cornea. Particle size also affects the dissolution rate.
The time required for dissolution & corneal absorption must be less than the residence time of the drug in the conjunctival sac to take advantage of the retained particles. The saturated solution of suspension provides initial response, whereas the retained particles maintain the response as particle dissolve & drug is absorbed.
With the decrease in the particle size bioavailability increases. Three suspensions of dexamethasone with particle sizes 5.75, 11.5 & 22 micrometer exhibit increasing blood levels with decreasing particle size when instilled into the eyes of rabbit.
The particle size must be small enough to prevent corneal abrasion, because mild irritation can induce lacrimation & facilitate drug removal.
Label should state, “ shake well before each use”.
Contact time of ophthalmic preparations is of primary importance because otherwise significant drug abs. cannot take place.
Ophthalmic ointments provide long contact time as compared to viscous solution so used preferably.
Ocular bioavailability of chloramphenicol ointment & solution was compared & it is found that the ointment prolong the drug concentration in aq. Humor above the minimum effective concentration while solution had to be instilled every 15 min. to attain comparable drug levels, which rapidly fall when the instillation were discontinued.
Studies also report that increase in viscosity of vehicle retard drainage & promote contact time with the cornea due to increase in contact time hydrophilic drugs show greater improvement in ocular bioavailability.
Administration of drug solution or suspension by rectum is accomplished with an enema system. Enemas are large in volume (50- 100ml) have limited patient acceptability & used in disease state which directly affect the colon e.g. ulcerative colitis.
When carbamazepine administered as rectal suspension show low bioavailability as compared to oral suspension of carbamazepine. It is likely that slow dissolution of hydrophobic carbamazepine limited their bioavailability.
Bioavailability of Phenobarbital & Phenobarbital sodium was observed from different suppository bases. Result indicated that drug release from suppository base was not rate limiting rather drug permeability across the rectal tissues was controlling the bioavailability of Phenobarbital.
Usually drug incorporated into rapidly dissolving water-soluble bases result in higher bioavailability than do the fatty bases.