I would like to ask more about drug delivery system. Actually, I am PhD student in Japan and do research about carbon nanotube and their application in drug delivery system. Now I try to put drug and magnetic material inside carbon nanotube. I will inject them into blood stream. I expect magnetic material will be induced by outside magnetic field to bring carbon nanotube and drug to therapeutic site. My problem is "I dont know exactly propose of drug delivery system ". It is just bring drug to target site, reduce the side effect from drug and "is it important to protect drug from the blood environment?". I just want to know most kind of drug travelling in blood stream need protection from hydrolysis or enzymatic in blood stream. I read a lot of papers but I can not be clarified. I don't know how important to protect drug from blood environment. If possible, Give me the paper or some information that answer my question

Just something I asked some one and they gave me this hope it can help... at least give you an direction... [QUOTE]Methods for evaluating the in vivo fate of solid dosage forms. Application to gastroretentive dosage forms and colonic drug delivery systems.


Prof.A.J.Moes, Laboratory of Pharmaceutics and Biopharmaceutics, Université Libre de Bruxelles, Campus Plaine, C.P.207, 1050 Brussels, Belgium.

This presentation begins with gamma scintigraphy which is a non-invasive method used to follow the gastrointestinal transit of solid dosage forms, particularly non-disintegrating single-unit and multiple-unit sustained-release forms

After a brief description of the basic principles underlying gamma scintigraphy, including the detection of three radionuclides simultaneously, typical determinations of the gastrointestinal transit of non-disintegrating dosage forms are discussed.

Determination of various events carried out by direct visualization of dosage forms in the GI tract (qualitative determinations)

Gastric Residence Time (GRT) of single-unit non-disintegrating dosage forms (delineation of the stomach at the beginning and at the end of the session).
Mouth to caecum Transit Time (MCTT) of single-unit non-disintegrating dosage forms.
MCTT - GRT = Small Intestinal Transit Time (SITT) of single- unit non-disintegrating dosage forms.
Stagnation time of large single-unit matrix systems at ileo-caecal junction
Colonic transit time of single-unit non-disintegrating dosage forms.
Intragastric relative height kinetics of floating and non-floating single-unit non-disintegrating dosage forms.
Fragmentation of large single-unit non-disintegrating dosage forms in the stomach and/or during gastric emptying.
Adhesion of single-unit non-disintegrating dosage forms to the gastric mucosa and/or to each other.
Labelling of the so-called radiotelemetry capsule with a gamma emitting radionuclide enables its location in the gastrointestinal tract, hence allows the recording of in vivo pH values according to the GI sites.
Quantitative determination of various events carried out by measuring the radioactivity of ROIs vs. time.

Lag time for gastric emptying of multiple-unit dosage forms.
t50% gastric emptying (t50% GRT) of multiple-unit dosage forms.
Gastric emptying of test meals.
Simultaneous determination of gastric emptying of meals and 50% GRT of multiple-unit dosage forms.
Mouth to Caecum 50% transit time (MCTT) of multiple-unit dosage forms.
50% MCTT - 50% GRT = 50% Small Intestinal Transit Time (50% SITT) of multiple-unit dosage forms.
50% Colonic Transit Time of multiple-unit dosage forms.
Determination of the disintegration time of conventional solid dosage forms in the stomach.
Relevant information collected from gamma scintigraphy studies on the behaviour of solid oral sustained-release dosage forms during their GI transit.

In fasting conditions, the GRT of non-disintegrating monolithic dosage forms (coated tablets, matrix tablets, osmotic tablets, hydrophilic matrix capsules... ) is highly variable and totally umpredictable (10 to 120 minutes). It depends on the coincidence of dosing with the occurrence of the IMMC phase III. The GRT of such single-unit forms may be as long as 10 hours when they are dosed after a high fat meal (the GRT enhancement depends on the calorific value of the meal).
In fasting conditions, pellets are rapidly emptied from the stomach as a bolus. When these multiple-unit dosage forms are given after a meal, the GRT enhancement is smaller than that observed for monolithic forms, as due to their small size, pellets can be emptied from the stomach during the digestive phase. Like for meals, the gastric emptying of pellets is generally a first order rate process so that it may be characterized by the half emptying time (t50% GRT).
When administered just after a meal, the gastric emptying of multiple-unit forms is slower than that of the meal components and starts generally after an unpredictable lag time.
The gastric emptying profiles of pellets and other multiple-unit dosage forms allow to understand why the gastric transit of these forms is more even than that of monolithic dosage forms which is a all or nothing phenomenon.
The small intestinal transit of pharmaceutical dosage forms is remarkably short (3 ± 1 h) and constant, irrespective of the fed or fasted state of the subjects and of the type of dosage form ingested.
Stagnation of large single-unit matrix delivery systems is often observed at the ileocaecal region. This phenomenon is highly variable (1-12 h) and unpredictable. It never happens with multiple-unit dosage forms
Consequences

the gastric emptying rate of non-disintegrating dosage forms is dramatically influenced by the way of dosing, either during the digestive phase (fed conditions) or during the interdigestive phase (fasted conditions)

The gastric emptying being the first significant event of the GI transit, the GRT determines the total duration of the GI transit.

When drugs are given in fed conditions, liquids and solids having a diametral size smaller than 5 to 7 mm (particulate dosage forms, pellets, small tablets and capsules) can still be emptied from the stomach because their size is smaller than that of the pyloric opening but their gastric emptying may be dramatically delayed (lag time whilst food emptying proceeds).

On the contrary, in these conditions, large size single-unit delivery systems cannot be emptied and have to await for the onset of IMMC at the beginning of the interdigestive phase to be cleared from the stomach.

The behaviour of the various delivery systems in the GIT being different as a function of the way of dosing, namely in fasting or non-fasting conditions, the latter may influence significantly the drug release characteristics from the dosage forms, especially when the release properties depend strongly on pH, whatever the reasons for this pH-dependence (solubility of drugs according to pH and/or formulation concept of dosage forms).

Variation in drug absorption performances may happen also with dosage forms characterized by pH-independent drug release patterns. In these cases, the variations observed depend essentially on the total duration of the GI transit : the longer the GI transit duration, the higher the fraction of the dose of drug absorbed.

From all these observations, we can conclude that one can hardly rely on a predictable and reproducible time span to define the delivery life-time of solid oral controlled-release dosage forms.

Thus, it appears that the drug absorption in the GI tract may be highly variable since the period available for drug delivery completion is unpredictable and may be very short in certain circumstances.

These limitations related to GI transit indicate that there should be a major interest to retain sustained-release delivery systems in the stomach for a prolonged and predictable period.

Targeted drug release in the stomach can also be attractive for several reasons:

better dissolution of weak bases which are poorly soluble at higher pH;
any solute released in the stomach will empty together with fluids and will have the whole surface of the intestine available for absorption. This should be particularly useful when an absorption window exists in the proximal small intestine (e.g. riboflavine, levodopa);
positioned gastric release appears also to be useful for all substances intended to produce a lasting local action onto the gastroduodenal wall.
Limitations : drugs poorly soluble and/or unstable in the gastric environment, drugs irritating to the. Gastric mucosa, enteric coated systems, drugs for selective delivery in the colon.

Proposed means for prolonging the GRT of drug delivery systems.

1. The use of large single-unit dosage forms administered after a calorific meal which have to wait for the completion of the digestive phase to be cleared from the stomach under the influence of phase III IMMC activity.

Drawbacks

- possibility of permanent retention of rigid large size single-unit forms.

Subjects at risk: those who had bowel obstruction, intestinal adhesion, gastroplasty or simply who have a narrow pyloric opening (mean resting pyloric diameter: 12.8 ± 7.0 mm).~

- fragmentation of large size, soft hydrophilic matrices under the action of antral peristaltic waves during the digestive phase and/or before gastric emptying, under the action of phase III IMMC activity. Consequences: fragmentation into smaller pieces may not only impede the expected GRT enhancement but may alter also the initially programmed drug release kinetics.

These two papers might help, although I hope you are Dr. Somlak by now =)

Riviere JE. Pharmacokinetics of nanomaterials: an overview of carbon nanotubes, fullerenes and quantum dots. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2009 Jan;1(1):26-34. PMID: 20049776

Lacerda L, Bianco A, Prato M, Kostarelos K. Carbon nanotubes as nanomedicines: from toxicology to pharmacology. Adv Drug Deliv Rev. 2006 Dec 1;58(14):1460-70. Epub 2006 Sep 30. PMID: 17113677