Excipient absorption

Bioavailability, Bioequivalence, and Pharmacokinetics. Bioavailabihty can be defined as the amount and rate of absorption of a dmg into the body from an adrninistered dmg product. It is affected by the excipient ingredients in the product, the manufacturing technologies employed, and physical and chemical properties of the dmg itself, eg, particle size and polymorphic form. Two dmg products of the same type, eg, compressed tablets, that contain the same amount of the same dmg are pharmaceutical equivalents, but may have different degrees of bioavailabihty. These are chemical equivalents but are not necessarily bioequivalents. For two pharmaceutically equivalent dmg products to be bioequivalent, they must achieve the same plasma concentration in the same amount of time, ie, have equivalent bioavadabihties. 

Co-administration of ofloxacin and chitosan in eyedrops increased the bioavailabUity of the antibiotic [290]. Trimethyl chitosan was more effective because of its solubility (plain chitosan precipitates at the pH of the tear fluid). On the other hand, N-carboxymethyl chitosan did not enhance the corneal permeability nevertheless it mediated zero-order ofloxacin absorption, leading to a time-constant effective antibiotic concentration [291]. Also W,0-carboxymethyl chitosan is suitable as an excipient in ophthalmic formulations to improve the retention and the bioavailability of drugs such as pilocarpine, timolol maleate, neomycin sulfate, and ephedrine. Most of the drugs are sensitive to pH, and the composition should have an acidic pH, to enhance stability of the drug. The delivery should be made through an anion exchange resin that adjusts the pH at around 7 [292]. Chitosan solutions do not lend themselves to thermal sterilization. A chitosan suspension, however. 

This technique has also been used in combination with nitrogen absorption to study the pore structure of some excipients, particularly MCC in both the powdered and compacted state. The intraparticulate porosity of MCC has been shown to be unaffected by tableting the interparticular pores, however, are gradually reduced in size [38]. Recently this method has been used to evaluate the internal structure of tablets prepared from microcapsules [150]. 

Solvents used to increase solubility for compounds during screening of permeability across the cell monolayers, together with commonly used excipients for formulations, can also affect the barrier as they contain ingredients which enhance drug absorption [100, 151]. There are different mechanisms by which these compounds can modulate the barrier [4, 149, 150] for example, they may increase the tight junctional pathway inhibiting carrier-mediated transport, or cholesterol... 

Such requirements are expected to assure that the dosage form is formulated and manufactured appropriately to ensure that the index or marker ingredients are uniformly distributed and will dissolve in the gastrointestinal tract and be available for absorption. No assumption is made that the marker or index compound selected for demonstration of dissolution is responsible for the purported effect. The test is valuable in that it assures that the formulation technology used is reflective of the state-of-the-art technology, provides a means to evaluate lot-to-lot performance over a product s shelf-life and that excipients used to facilitate transfer of the index or marker ingredients of the botanical to the human system are appropriate. 

The solubility of C60 and C70 fullerenes in vegetable oils will permit to employ these molecules for topical use in creams, lotions and ointments, which are adsorbed by skin. Vegetable oils, especially olive oil, are considered excellent excipients for injectable preparation where the active principle is soluble in fats. Their absorption in the subcutaneous tissues is slow and limited and ensures a gradual release of the active principle (Adami, 1960). 

The intercellular route is considered to be the predominantly used pathway in most cases, especially when steady-state conditions in the stratum corneum are reached. In case of intercellular absorption, substance transport occurs in the bilayer-structured, continuous, intercellular lipid domain within the stratum corneum. Although this pathway is very tortuous and therefore much longer in distance than the overall thickness of the stratum corneum, the intercellular route is considered to yield much faster absorption due to the high diffusion coefficient of most drugs within the lipid bilayer. Resulting from the bilayer structure, the intercellular pathway provides hydrophilic and lipophilic regions, allowing more hydrophilic substances to use the hydrophilic and more lipophilic substances to use the lipophilic route. In addition, it is possible to influence this pathway by certain excipients in the formulation. 

A linearization of the steady-state concentration gradient could be demonstrated by relating the depth to the weight of the tissue, removed per piece of adhesive tape. However, large errors, especially, within the first tapes, cast doubt over these findings [127, 128], The procedure is time-consuming and artifacts, due to absorption and desorption of moisture, formulation excipients, or sebaceous lipids, are likely. 

Currently, most strategies for buccal delivery of peptide drugs have focused on the application of excipients that would shorten the time of absorption and adhere drugs to a local site on the mucosa, thus decreasing exposure to proteolytic degradation and possible release of drug back into the mouth cavity. This strategy has been utilized in the buccal delivery of insulin, enkephalin, and testosterone [37, 70]. 

Table 18.2 Caco-2 permeability and human absorption of 28 marketed drugs and excipients.

The Committee for Proprietary Medicinal Products [8] applied the BCS, with certain requirements, to dispense with bioequivalency tests if the active pharmaceutical ingredient is class I and the in vitro dissolution of the finished dosage form is fast [9], An active substance is considered highly soluble if the amount contained in the HDS of an IR product is dissolved in 250 ml of each of three buffers within the range of pH 1-8 at 37°C (e.g., pH 1.0, 4.6, and 6.8). There should be linear and complete absorption, which indicates HP to reduce the possibility of an IR dosage form influencing the bioavailability [8], The similarity of the dissolution profiles of the test and reference products is demonstrated in each of three buffers within the range of pH 1-8 at 37°C (e.g., pH 1.0,4.6, and 6.8). If there is rapid dissolution of the product, where at least 85% of the active substance is dissolved within 15 min, no further comparison of the test and reference is required. Further requirements include that excipients be well established and have no interaction with the pharmacokinetics of the active substance and that the method of manufacture of finished product... 

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