PubMed · 4101267
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H J Richards. 1971-03-27. Myocrisin.. https://pubmed.ncbi.nlm.nih.gov/4101267/
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Herbal drug formulation is a challenge in pharmaceutical technology due to the complex physicochemical properties of these multicomponent materials. Potential instabilities of the pharmacologically active and coactive substances as well as incompatibilities and interactions of the extracted compounds and excipients have to be considered. Microbial contamination of the applied plant material might limit the shelf life of the products. Using state of the art methods in formulation stable preparations are obtained; additionally compliance of drugs might be enhanced due to simplified application or better sensorial quality. Nowadays, besides traditional pharmacopoeial aqueous, ethanolic, or (partially) dried extracts fluid, semisolid, or solid dosage forms of these extracts are in use, for example syrups, juices, drops, liniments, gels, ointments, creams, suppositories, tablets, coated tablets (dragees) as well as soft and hard gelatine capsules.
In 1958, F.H. Dost [1958] defined the mean life-span ("mittlere Lebensdauer") of a total number of N molecules as the arithmetic mean of all times "z(i)" of any one of the N molecules residing in a pharmacokinetic system. This pharmacokinetic characteristic did not attract special interest for several years. Almost simultaneously Yamaoka et al. [1978], Cutler [1978], van Rossum [1978], Benet and Galeazzi [1979], and von Hattingberg and Brockmeier [1979] recommended the mean residence time (MRT) or mean time (MT) as a useful summarizing characteristic for complex pharmacokinetic systems. One of the most useful properties of the statistical analysis (also called "moment analysis" or "statistical moment analysis") of concentration-time data and in vitro dissolution profiles using moments is the additivity of mean times [von Hattingberg and Brockmeier 1978, 1979]. The very simple and compelling logic of additivity can be explained by the following example: considering an oral administration of a readily available dosage form, the distribution of each individual molecule within the body and the elimination from the body must be preceded by absorption of this molecule, which is trivial. However, as a consequence, the total transit time of an individual molecule through this system is the sum of its time up to absorption into the central circulation z(i).abs and the time the molecule spends in any part of the volume the molecule can reach z(i).vss. Therefore, the total mean time of all drug molecules available is the sum of the mean absorption time MT(abs) and the mean time in the steady-state volume of distribution MTvss. It is obvious that we can estimate the two components of the total mean time, i.e. MTabs and MTvss, by an appropriate experimental setting giving the drug once intravenously and determining MTvss and once giving the drug as an oral solution and deducing MTabs = MTtotal - MTvss. Because of this very useful property of the statistical analysis of concentration-time data by moments, this approach has been entitled "component analysis" [von Hattingberg et al. 1984].
The main purpose of this study was to determine the influence of factors (pH, enzymes, etc.) chosen partially to mimic in vivo conditions on the release of a model drug, indium oxine, from polyepsiloncaprolactone (PCL) nanocapsules in vitro. A nanocapsule suspension, an emulsion (O/W), and a solution in olive oil were prepared in order to compare the release of a radioactive tracer, indium oxine, as a function of time by an in vitro dialysis method. Nanocapsules were prepared by interfacial deposition of PCL and characterized by particle size distribution (laser light scattering) and determination of the polymer molecular weight by gel permeation chromatography (GPC). The results of this study suggest that the partition coefficient between the acceptor medium and the olive oil is the major parameter governing the release of the isotope, at least in the absence of significant enzyme activity. The PCL wall of nanocapsules is a barrier that does not seem to retard the release of indium. The addition of porcine liver esterases accelerated the degradation of PCL. This study confirms that the release of a drug from nanocapsules may be very different depending on the in vivo location, that is, the administration site.