Biphasic drugs

Lenaerts et al. (2) prepared a biphasic drug delivery device for tramadol consisting of polyvinyl acetate and polyvinylpyrrolidone having a sustained release for 24 hours. Polyvinylpyrrolidone was also used by Midha et al. (3) in the trans-dermal delivery of atomoxetine. 

Ofori-Kwakye, K., and Fell, J. T. (2003), Biphasic drug release from film-coated tablets, Int. I. Pharm., 250,431-440. 

Pectin has been used in film-coating formulations containing chitosan and hydroxypropylmethyl cellulose in the investigation of the biphasic drug-release properties of film-coated paracetamol tablets, both in vitro and in vivo It has been shown that chitosan acts as a crosslinking agent for concentrated pectin solutions. 

Ofori-Kwakye K, Fell JT. Leaching of pectin from mixed films containing pectin, chitosan and HPMC intended for biphasic drug delivery. Int J Pharm 2003 250(1) 251-257. 

Dose-effect curve for a biphasic drug effect... 

Nicotine is called a biphasic drug because at low doses it stimulates ACH receptors but at higher doses it retards neural transmission (Taylor, 2001). This biphasic action partly e. plains the complex effects that humans perceive when they ingest nicotine, which we discuss shortly. 

Jiang, Y.-N., Mo, H.-Y, and Yu, D.-G. (2012) Electrospun drug-loaded core-sheath PVP/zein nanofibers for biphasic drug release. Int. J. Pharm., 438, 232-239. 

At higher concentrations than 100 yM an inhibition of PA conversion into DG results. However at concentration of 10 yM a decrease in IPG labeling from C-glycerol takes place and an enhanced flow of radioactivity towards CPG, EPG and TG occurs. Thus two different mechanisms are needed to explain these observations. Both stimulatory and inhibitory actions on the phosphatidate phosphatase are suggested to account for the biphasic drug action as well as opposite effects on the conversion of PA in IPG take place (Table 3). 

Biphasic Drug delivery methods Micro/Nano emulsions. 

Fan LF, He W, Bai M, Du Q, Xiang B, Chang YZ, Gao DY. Biphasic drug release Permeability and swelling of pectin/ethylcellulose films, and in vitro and in vivo correlation of film-coated pellets in dogs. Chem Pharm Bull (Tokyo). 56 (8) 1118-1125,2008. 

There are similarities between the biological actions of inhalants and those of alcohol and barbiturates (Bowen et al. 1996b). For example, acute administration of inhalants affects motor coordination (Moser and Balster 1981) and induces anxiolysis, whereas chronic administration is associated with physical dependence and withdrawal (Bowen et al. 1996a Evans and Balster 1991, 1993). In addition, some inhalant drugs have anticonvulsant properties (Wood et al. 1984). Like other CNS-depressant agents, inhalants have biphasic effects on spontaneous locomotor activity in rodents, with increased activity seen at lower doses and diminished locomotion seen at higher doses (Cause et al. 1985 Kjellstrand et al. 1985). 

Recently, Brich and coworkers (40) reported the synthesis of lactide/glycolide polymers branched with different polyols. Polyvinyl-alcohol and dextran acetate were used to afford polymers exhibiting degradation profiles significantly different from that of linear poly-lactides. The biphasic release profile often observed with the linear polyesters was smoothened somewhat to a monophasic profile. Further, the overall degradation rate is accelerated. It was speculated that these polymers can potentially afford more uniform drug release kinetics. This potential has not yet been fully demonstrated. 

Both processes used to manufacture microspheres produce relatively porous structures. Consequently, release of drugs is generally biphasic, with an initial fast release phase followed by a slower... 

In a series of papers, Gupta et al. (109-112) studied the in vitro release properties of heat-stabilized BSA microspheres containing adriamycin. The biphasic release of drug was attributed to its location in the microsphere. The initial release results from surface desorption and diffusion through pores, while the later release arises from drug within the microsphere, which becomes available as the microsphere hydrates. 

COMMENT/QUESTION 1 was very intrigued by your substitution data from the drug discrimination paradigm. But my question is not unlike Lou Seiden s. For with substances that are characterized by tremendously qualitatively different effects, biphasic in nature, and in many functional... 

If two different types of K conductances contribute to component S, we might anticipate that some drugs will affect the two conductances differently. Indeed, the dose-response curves for inhibition of S by tetra-alkylamines and 4-AP appear to be biphasic (Bartschat and Blaustein 1985a), which is consistent with this prediction. The obviously biphasic dose-response curve for PCP inhibition of component S (figure 2, open circles) provides further evidence for this view. 

Various factors that influence the release of drugs from particulate carriers are listed in Table 10. Drugs can be released by diffusion or by surface erosion, disintegration, hydration, or breakdown (by a chemical or an enzymatic reaction) of the particles. The release of drugs from microspheres follows a biphasic pattern that is, an initial fast release followed by a slower... 

Thompson, G.A., J. Smithers, and H. Boxenbaum. 1990. Biphasic mortality response of chipmunks in the wild to single doses of ionizing radiation toxicity and longevity hormesis. Drug Metabol. Rev. 22 269-289. 

Peak plasma levels are reached about 1.5 h after oral ingestion, the maximum concentrations being in the order of 2 - 3 ng equivalents/ml (parent drug + metabolites) for an oral 1 mg dose. The elimination from the plasma is biphasic and proceeds with mean half-lives of 6 h (a-phase) and 50 h ((3-phase). Similar elimination half-lives are obtained from the urinary excretion. The cumulative renal excretion is practically the same after oral and intravenous administration and amounts to 6 - 7 % of the radioactivity dosed. The main portion of the dose, either oral or intravenous, is eliminated by the biliary route into the faeces. The kinetics of bromocriptine has been demonstrated to be linear in the oral dose range from 2.5 to 7.5 mg. 

Phenol red is rapidly cleared biphasically from the plasma compartment with an initial t of about 46 min. (Fig. 3) and a second phase with a t of 8 3 hrs. As early as 10 min. there are detectable levels or phenol red in the kidney. The concentration of drug in kidney peaked at 30 min. and decayed with a half-time of about 9 hrs. There also were detectable levels of phenol red within 10 min. in liver but the values were considerably below those of plasma and kidney. Hepatic levels took longer (ca. 2 hrs.) to peak than did those in kidney, and then decayed with a half-time of about 10 hrs. The glucuronide... 

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