Matrix transdermal system

B. Scale-Up Studies, Demonstrations, and Trials for Matrix Transdermal Systems... 

Passive transdermal dehvery systems on the market tend to be either matrix or membrane controUed. In matrix devices, the stmctural and molecular characteristics of the dmg-polymer matrix determine dmg release. Examples of polymer matrix-controUed diffusional systems for angina prophylaxis include Nitro-Dur and Nitrodisc, which provide transdermal dehvery of nitroglycerin [55-63-0], and Erandol, a tape that releases isosorbide dinitrate [87-33-2]. Matrix diffusional systems have been used for dehvering dmgs with a wide therapeutic index. 

V.a.1.2. Transdermal preparations. Adhesive patches applied to the skin can be used to deliver oestrogens transdermally, using either a reservoir of liquid or an oestradiol-containing matrix. These systems deliver adequate amounts of oestradiol to maintain plasma levels within the normal range for 24 hours, and some preparations now provide transdermal progestagen also, thus avoiding the need for additional tablets to be taken for part of the cycle. 

Andersson TL, Stehle B, Davidsson B, Hoglund P. Bioavailability of estradiol from two matrix transdermal delivery systems Menorest and Climara. Maturitas 2000 34(l) 57-64. 

Manufacturing routes for matrix and reservoir transdermal systems. 

Cal, K., S. Janicki, and M. Sznitowska. 2001. In vitro studies on penetration of terpenes from matrix-type transdermal systems through human skin. Int J Pharm 224 81. 

As with oral diffusion-controlled systems, there are two basic designs for transdermal diffusion-controlled systems matrix-type and reservoir-type systems. The matrix-type systems can be further classified as... 

There is a wide variety of transdermal systems on the market at present. These patches are diversely referred to as reservoir , monolithic , membrane-controlled , adhesive , matrix , and so on. Unfortunately, these terms are not always used consistently and, worse, they are sometimes used inaccurately. In all cases, however, the idea is that the system offers a means to hold a payload of the drag and a configuration (or platform ) to ensure presentation of the active agent to the skin surface at a rate sufficient to ensure a systemic pharmacological effect after the drag has crossed the skin s barrier. Most simplistically, one can divide the transdermal formulations presently available into three categories (Figure 8.3) ... 

Daytrana is a newly approved methylphenidate transdermal system. It is a 9-h adhesive matrix patch and comes in four sizes a 12.5-cm2 patch that has a delivery rate of l.lmg/h, an 18.75-cm2 patch that has a delivery rate of 1.6mg/h, a 25-cm2 patch that delivers 2.2mg/h, and a 37.5-cm2 patch that delivers 3.3mg/h. 

Baracat, E. Yamada, S. Haidar, M. Rodrigues De Lima, G. Peloso, U. Benedictis, E. Casoy, J. Evaluation of skin tolerabihty in patients on a 7-day regimen of a new matrix transdermal estradiol dehvery system an open-label study. Curr. Ther. Res. 1997, 58, 417 27. 

Ethylene vinyl acetate copolymers are used as membranes and backings in laminated transdermal drug delivery systems. They can also be incorporated as components in backings in transdermal systems. Ethylene vinyl acetate copolymers have been shown to be an effective matrix and membrane for the controlled delivery of atenolol triprolidine, and furose-mide. The system for the controlled release of atenolol can be further developed using ethylene vinyl acetate copolymers and plasticizers. ... 

Rgure 9.27 The four main types of transdermal patch matrix, reservoir, multilaminate and drug-in-adhesive designs. The matrix/reservoir systems are cut away to show the drug. Illustration courtesy of 3M. 

Scheme 2 Some possibilities for the pharmaceutical technologies and approaches to be used in personalized medicine, ranging from simple liquid oral dose forms where the dose can be varied by volume, through responsive systems, micro-electromechanical systems (MEMS), GPS-directed systems (see text) transdermal systems, thin film technologies with passive or active release mechanisms, combination tablet or capsule dose forms, and what we term dosed solid platforms, for example, aqueous dispersible polymer, solid gel or matrix material into which precise doses of drag can be absorbed.

The microsealed delivery device is a variation of the matrix-type transdermal system in which the drug is dispersed in a reservoir phase which is then immobilized as discrete droplets in a cross-linked polymeric matrix. Release can be further controlled by inclusion of a polymeric microporous membrane. This system therefore combines the principles of both the liquid reservoir and matrix-type devices. Rate of release of a drug from a microsealed delivery system is dependent on the partition coefficient between the reservoir droplets and the polymeric matrix the diffusivity of the drug in the reservoir, the matrix and the controlling membrane and on the solubility of the drug in the various phases. There are, obviously, many ways to achieve the desired zero-order release rate, but only nitroglycerin has been commercially formulated into this type of delivery device (Karim 1983). 

Manufacturing processes for reservoir, matrix and drug-in-adhesive transdermal systems are largely similar and involve the following stages ... 

There are two designs in transdermal systems membrane-controlled systems and matrix systems. A brief discussion of the features of each is given below. 

When response to a chemical is strong due to favorable ionization properties of the substance, mobility spectrometers can often provide direct monitoring without effects from potential interferences in the sample matrix. This was seen with the evaluation of nicotine emissions at a production site for transdermal systems (i.e., skin patches) for treating nicotine withdrawal. Nicotine patches are prodnced by depositing drops of nicotine onto an adsorbent layer that is drawn as a continuous... 

Matrix transdermal drug delivery system in which a therapeutic agent is dispersed/dissolved in the adhesive layer... 

Matrix transdermal drug delivery system based on an island dressing design [adapted from Chien 1992 (a.47)l... 

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