Adsorption Glyceryl Trinitrate

Figure 10.17 Plasma concentrations of rifampicin (RMP) after oral administration in solution (10 mg kg 1) given alone (A), with p-aminosalicyclic acid (PAS) granules (•), or with Na-PAS tablets (O); mean values (n = 6 patients) are indicated.

Reproduced from reference 23.

(section 8.3.7) discussed the adsorptive loss of insulin from solution; adsorption can be a problem because of the amphipathic nature of many peptides, and becomes pharmaceuti-cally important when they are present in low concentrations in solution. The adsorption of peptides onto glass has been ascribed to bonding between their amino groups and the silanol groups of the glass. A decapeptide derivative of LHRH, the natural luteinising hormone releasing hormone, has two basic amino groups positively charged at low pH, providing an opportunity for binding to silanol groups.24 Siliconisation of the glass did not inhibit adsorption completely, suggesting that ionic binding was not the only mechanism of interaction. Phosphate buffer at 0.1 mol dm 3 concentration and acetate ions at 0.16 mol dm 3 concentration (both at pH 5) were most effective in preventing adsorption.

10.8 Drug interactions with plastics

In section 8.3.7 we discussed the adsorption of insulin on to glass and plastic materials used in syringes and giving sets. The plastic tubes and connections used in intravenous containers and giving sets can adsorb or absorb a number of drugs (Fig. 10.18), leading to significant losses in some cases. Those drugs which show a significant loss when exposed to plastic, in particular poly(vinyl chloride) (PVC), include insulin, glyceryl trinitrate, diazepam, chlormethiazole, vitamin A acetate, isosorbide dinitrate and a miscellaneous group of drugs such as phenothiazines, hydralazine hydrochloride and thiopental sodium.

Adsorption of drug to plastic

Adsorption of proteins to syringe

Partitioning of drug into plastic

Adsorption of drug to plastic

Adsorption of proteins to syringe

Partitioning of drug into plastic

Figure 10.18 The possible modes of interaction between a drug and the plastic of a giving set.

Leaching of plasticiser into formulation

Figure 10.18 The possible modes of interaction between a drug and the plastic of a giving set.

A theoretical treatment to account for the loss of glyceryl trinitrate from solution to plastic containers has been developed, 25 see Box 10.1.

Some idea of the rate and extent of disappearance of warfarin sodium from PVC infusion bags can be gained from Fig. 10.19. The marked effect of pH is seen. Losses can

Box 10.1 Adsorption of glyceryl trinitrate onto plastic containers

Considering a two-stage loss of drug:

A4b 2 C

Where A = Glyceryl trinitrate in aqueous solution Where B = Adsorbed glyceryl trinitrate Where C = Glyceryl trinitrate dissolved in the matrix

Therefore,

It is found that dB/dt>> dC/dt. At steady state,

dB/dt # 0, and at t # 0, A # A0, B # 0 and C # 0. Rate constant k1 is a function of the amount of drug in solution, the surface area available for adsorption and the nature of the plastic, and k3 is a function of the volume of the plastic matrix and the solubility of the glyceryl trinitrate in the plastic matrix. The ratio k3/k2 describes the partitioning of the drug between the plastic and the aqueous phase. So, if P is the partition coefficient, k3 P

a being a proportionality constant related to the mass of the plastic, the volume of the solution and other parameters. The ratio k1/k2 can be related to a Langmuir type of adsorption constant.

The final form of the equation accurately predicts the glyceryl trinitrate remaining in solution (A):

0 50 100 150 200

Figure 10.19 Disappearance of warfarin sodium from aqueous buffered solutions stored in 100 cm3 PVC infusion bags at room temperature.

Reproduced from reference 26 with permission.

0 50 100 150 200

Figure 10.19 Disappearance of warfarin sodium from aqueous buffered solutions stored in 100 cm3 PVC infusion bags at room temperature.

Reproduced from reference 26 with permission.

Table 10.8 Loss of drugs from normal saline solutions in poly(vinyl chloride)(PVC) bags stored at 22°C for 8 ha

Drug

Initial solute conc.

0 0

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