Pulsed release

Photolysis of the 2-fluorenyl azide precursor compound by the 267 nm pump laser pulse releases a nitrogen molecule and produces the singlet 2-fluorenylnitrene intermediate as shown in Scheme 3.2. In the presence of appreciable amounts of water, this singlet 2-fluorenylnitrene species can react with the water molecule to form a singlet 2-fluorenylnitrenium ion and an OH species as shown in Scheme 3.2. 

The dispersion coefficients are dependent on the character of the media and the flow velocity. It is difficult to predict these coefficients within an order of magnitude, so they are normally measured or fit to measured data in the field. For example, if a concentration variance in the x-, y-, and z-directions can be measured in response to a pulse release, then equation (6.51) could be applied to obtain... 

A new ibuprofen pulsed release oral dosage form... 

Preliminary in vivo experiments carried out on this biphasic pulsed release device containing ibuprofen as a model drug reveal two distinct peaks in plasma profiles, thus indicating that the in vitro results are in good agreement with the in vivo blood levels. 

Taking all these considerations into account, the aim of this work was to design and prepare a new pulsed release oral drag delivery system, capable of releasing an immediate dose of drag as well as a further dose after some hours. 

To obtain such a pulsed released pattern, a system based on a three-layer tablet with the following characteristics has been designed. 

A NEW IBUPROFEN PULSED RELEASE ORAL DOSAGE FORM 81... 

Fig. 1—Schematic representation of the prepared pulsed release system a, layer containing the immediately available dose of drug (first dose) b, barrier of swellable polymeric material c, layer containing the second dose of drug d impermeable film container.

On in vitro testing when the pulsed release system is immersed in the dissolution medium, the following can be observed ... 

Fig. 5 shows an example of the plasma levels after administration of the pulsed release system to two volunteers. As can be seen from Fig. 5, in both cases there are two peaks. The first peak is 20pg ml-1 after about lh, and the second is 16-20 pg 1 after 4.5-5 h there is an evident delay in the absorption of the second dose which appears to correlate quite well with the in vitro performance of the pulsed system. 

Fig. 5—ibuprofen plasma levels following administration of pulsed release system to two subjects , first subject . second subject. 

Despite the problems posed by the pharmacokinetic and physicochemical characteristics of ibuprofen (small therapeutic window, erratic absorption owing to its poor solubility, etc.), this pulsed release system results in good separation of the two plasma peaks (indicating that there is in fact delayed release of the second drug dose) at the desired concentrations. 

When the microencapsulated liposomes are left untreated the lipid bilayer provides a barrier to diffusion through which the entrapped protein does not pass until the liposomes gradually become leaky, primarily due to oxidation of the phospholipid side chains. This mechanism results in a delayed release. Triton or sonic treatment of the microencapsulated liposomes provide pulsed re ease. Since both detergent and sonication disrupt lipid bi ayers, the mechanism by which pulsed release is achieved may be that these stimuli initially disrupt the liposomes and then the lipid reforms around some of the protein solution inside the capsule, possibly in an altered lamellar form alternatively, the treatment could disrupt only the more susceptible liposomes, leading to two phases of release, first from the freed protein and later from protein that remained liposome-entrapped. 

Khoo, W. J. T. Veterinary implants for delayed pulsed release of antigen, in Proceed. Int. Symp. Control. Rel. Bioact. Mater., San Diego, CA, 1994, pp. 116—117. 

Figure 4. Potential-time curves from experiments with a thermopile heat conduction calorimeter. A A short heat pulse released at time t,. B A constant thermal power released between time t, and t2. The steady-state potential value, USI is proportional to the released thermal power.

The release location is determined by imposing a condition of causality upon the release history. Recovery of the source location and profile of the unit pulse release history with homogeneous parameters was used to demonstrate the method. Birchwood concluded that preliminary results suggest that the method is capable of quantifying the location coordinate of a pollution source to a reasonable degree of accuracy, but the results are highly sensitive to the accuracy of the inferred source location. 

The drug release studies were performed in HCl (pH 1.0) and phosphate buffer (pH 7.8) at an ionic strength 0.1 m/1. A pH dependent pulsed-release be-... 

Zhang, Y., Zhang, Z., and Wu,F. (2003), A novel pulsed-release system based on swelling and osmotic pumping mechanism,/. Controlled Release, 89,47-55. 

When the effects of time variations in release rates are included, pulse (or instantaneous) and continuous (plume) emissions are the two most common time-variant inputs in transport models. The classic example of a pulse release is a hazardous waste spill. The steady release of contaminants into groundwater from a subsurface contaminant and the continuous release of volatile solvents from an air-stripping tower are examples of plume emissions. 

Wilson, C.G. Bakhshaee, M. Stevens, H.N.E. Perkins, A.C. Frier, M. Blackshaw, E.P. Binns, J.S. Evaluation of a gastro-resistant pulsed release delivery system (pulsin-cap) in humans. Drug Deliv. 1997, 4 (3), 201-206. 

Wilding, I.R. Davis, S.S. Bakhshaee, M. Stevens, H.N.E. Sparrow, R.A. Brennan, J. Gastrointestinal transit and systemic absorption of captopril from a pulsed-release formulation. Pharm. Res. 1992, 9, 654—657. 

Administration of osmotic laxatives such as lactulose to healthy subjects increases defecation frequency, producing a reversible syndrome that mimics irritable bowel syndrome. Administration of 20 ml lactulose three times per day creates a more fluid environment as indicated by increased stool water content. To examine the effect of such an environment on drug delivery we administered pulse release units (Pulsincap) containing quinine dihydrochloride (50 mg) following treatment with lactulose for 3 days. ... 

Lee DY, Chen CM. Delayed pulse release hydrogel matrix tablet. United States Patent No. 6,103,263 2000. 

---