Tobramycin sulphate

Release kinetics of tobramycin sulphate from polymethylmethacrylate 171... 

Tobramycin sulphate (Nebcin , lot number 1CE30C) was donated by Eli Lilly Co., Indianapolis,... 

Three implants from each batch were assayed separately for tobramycin sulphate content by dissolving the PMMA in 45 ml of dichloromethane and extracting the tobramycin sulphate five... 

Tobramycin sulphate was determined spectrophotometrically using a derivatization procedure [6]. A 0.5-1 ml aliquot of the extracted solution was mixed with 1 ml of o-phthaldialdehyde reagent solution followed by addition of 1.5 ml of isopropanol to prevent precipitation. The volume was adjusted to 5 ml with distilled water and the absorbance was determined after 45 min on a Beckman DU-7 spectrophotometer at the maxima of 333 nm. The concentrations were obtained from a calibration curve of o-phthaldialdehyde-derivatized tobramycin. The assay had a coefficient of variation of less than 3% and a detection limit of 0.5 pg/ml. 

Dissolution kinetics was studied under sink conditions by placing one implant in varying volumes (usually 100 ml) of phosphate buffer pH 7.4, while agitating in a horizontally shaking water bath (50 1 rev/min) at 37 1°C. Samples were withdrawn at varying time intervals for a duration of 21 days (an estimate of the expected duration of clinical use) and the amount of tobramycin sulphate released was determined spectrophotometrically. Equal volumes of fresh medium were added to replace aliquots removed for assay and the amount of drug release was corrected for dilution. Triplicate measurements were performed for each batch of implants prepared. 

The influence of the following formulation factors on the release of tobramycin sulphate from PMMA carrier was studied ... 

Drug loading the drug-to-carrier ratio (tobramycin sulphate PMMA). Drug -carrier ratios (dry weight) of 1 33 (clinically used), 1 20, 1 10, and 1 5 were used. 

TOBRAMYCIN SULPHATE FROM POLYMETHYLMETHACRYLATE IMPLANTS 177 Table 2—Effect of formulation factors on computer-generated fast (a) and slow ) phase rate constants... 

Fig. 1—The effect of drug loading on tobramycin sulphate release profiles. The solid lines represent the lines of best fit.

The amount of tobramycin sulphate remaining unreleased from the PMMA implant after 1, 3 and 7 days in vivo is summarized in Table 3. The very low percentage of tobramycin sulphate released in vivo (10.57%) after 7 days supports the in vitro findings (18-20% released). 

Table 3—Tobramycin sulphate released in vivo wsing the osteomyelitic tibia rabbit model...

The release of tobramycin sulphate from non-biodegradable, spherical PMMA implants is biphasic and can be described by biexponential linear regression analysis. 

Although the release of tobramycin sulphate can be significantly improved with the addition of water-soluble additives such as polyethylene glycol 400, our current investigations are directed toward the design and development of biodegradable implants. 

Hombach J, Hoyer H et al (2008) Thiolated chitosans development and in vitro evaluation of an oral tobramycin sulphate delivery system. Eur J Pharm Sci 33 1-8... 

Administration devices for medicines used to treat asthma and COPD are prescriptirm products, with an exception for some nebulised (medicine) formulations. Medicines such as amphotericin B or antibiotics (coUstimethate sodium, tobramycin sulphate or gentamicin) for nebulisation in CF therapy are sometimes stUl partly prepared by hospital pharmacists, and so are nebulised solutions for bronchial challenge testing. Although product formulation and the method of preparation of formulations for inhalation are not the main subjects of this chapter, recommendations are given in the subparagraphs about nebulisation. 

Another example of a thiolated chitosan that has permeation-enhancing properties is chitosan-NAC, which showed an improvement in the uptake of tobramycin sulfate on Caco-2 cell monolayers of up to 2.7-fold in comparison to control tobramycin sulphate in buffer. A more pronounced permeation-enhancing effect could be achieved by the combination of 0.5% (m/v) chitosan-NAC and 0.5% GSH, giving an improvement ratio of 3.3 [51]. 

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