Release Of Gentamicin Sulfate Research Articles

Formulation of calcium phosphates/poly ( d, l-lactide) blends containing gentamicin for bone implantation

Implants to prevent or treat osteomyelitis are described, composed of phosphate/poly( d,l-lactide) blends containing the antibiotic gentamicin. Seven formulations of implants containing 3% gentamicin sulfate (GS) were prepared at 433 MPa and 693 MPa of compression pressure. The blends contained phosphates (25% hydroxyapatite (HAP), 75% tricalcium phosphate (TCP)) and 20% dl-PLA (weight average molecular weight, M w: 30 kD). To prolong GS release, implants were coated with PLGA ( M w:100 kD) or dl-PLA ( M w: 200 kD). Various durations of GS release from these devices were demonstrated as feasible. Release times of more than 10 weeks were attained with implants coated with dl-PLA ( M w: 200 kD), greatly exceeding the performance of the commercial formulation.

Evaluation of soluble Bioadhesive Ophthalmic Drug Inserts (BODI) for prolonged release of gentamicin: lachrymal pharmacokinetics and ocular tolerance.

The purpose of this investigation was the evaluation of Bioadhesive Ophthalmic Drug Inserts (BODI) for prolonged release of gentamicin sulfate (GS) in tears. The BODIs (length 5.0 mm, diameter 2.0 mm, weight 20.5 mg, average GS content 5.0 mg) were prepared by extrusion of a mixture based on hydroxypropylcellulose (HPC), ethylcellulose (EC) and carbomer. Two methods were tested to prolong the release of GS in tears: (1) preliminary treatment of GS and (2) use of a less hydrophilic polymer than HPC, hydroxypropylmethylcellulose (HPMC), as a vehicle constituent. The preliminary treatment consisted of the formation of a GS/cellulose acetate phthalate (CAP) solid dispersion (ratio GS/CAP: 10/6) made in acetonic medium, and in the coating of GS/EC granules (GS/EC ratio: 10/0.5) with an aqueous dispersion of CAP, to form a GS/EC/CAP coprecipitate (GS/EC/CAP ratio: 10/0.5/6). Inserts containing GS/CAP solid dispersion, GS/EC/CAP coprecipitate and HPMC resulted in improved time of efficacy (t(eff)) (43.8, 23.3, and 33.1 h, respectively), when compared to inserts containing GS without preliminary treatment (t(eff) = 11.9 h). A high irritation level was observed for inserts containing the GS/EC/CAP and HPMC. A relation between t(eff) and irritation score was established, emphasizing the importance of irritability as a factor during the evaluation of the potential of these systems.

Gentamicin-Loaded Hydraulic Calcium Phosphate Bone Cement as Antibiotic Delivery System

A hydraulic calcium phosphate cement made of β-tricalcium phosphate [β-Ca3(PO4)2], monocalcium phosphate monohydrate [Ca(H2-PO4)2·H2O], and water was used as a delivery system for the antibiotic gentamicin sulfate (GS). GS, added as powder or as aqueous solution, was very beneficial to the physicochemical properties of the cement. The setting time increased from 2 to 4.5min with 3% (w/w) GS and then slowly decreased to 3.75min with 16% (w/w) GS. The tensile strength increased from 0.4 to 1.6MPa with 16% (w/w) GS. These effects were attributed to the presence of sulfate ions in GS. The release of GS from the cement was measured in a pH 7.4 phosphate-buffered saline solution at 37°C by USP paddle method. Factors such as cement porosity, GS content and presence of sulfate ions or polymeric additives were investigated. The amount of GS released was roughly proportional to the square root of time up to ∼50% release. Afterwards, the release rate markedly slowed down to zero. In all but two cement formulations, the total dose of GS was released within 7days, indicating that no irreversible binding occurred between the cement paste and the antibiotic. When small amounts of hydroxypropylcellulose or poly(acrylic acid) were added to the cement, the maximum fraction released was a few percent lower than the total GS dose, suggesting some binding between the polymer and GS. The GS release rate was strongly influenced by the presence of sulfate ions in the cement paste and by the cement porosity. The higher the sulfate ion content of the cement paste, the lower the GS release rate. This influence was attributed to the finer cement microstructure induced by the presence of sulfate ions. Furthermore, when the initial cement porosity was increased from 38 to 69%, the release rate almost tripled (0.16 to 0.45h−1/2). Finally, the biological activity of GS in the cement was maintained, as measured by assaying the release medium.

Microencapsulation with carrageenan-locust bean gum mixture in a multiphase emulsification technique for sustained drug release.

A multiphase emulsification technique was modified in this process of micro-encapsulating gentamicin sulphate, thus avoiding the necessity for a surfactant in preparing the secondary emulsion for a W/O/W emulsion. Various proportions of iota-carrageenan (i-C) and locus bean gum (LBG) were investigated for the W/O/W emulsion after forming the primary W/O emulsion with sorbitan trioleate, Span 85. Upon removal of the oil phase (chloroform) from the W/O/W emulsion by heating (60-65 degrees C), microcapsules or 'W/W' particles containing drug dissolved in sodium hyaluronate were spontaneously formed. These were dispersed in a solution of a mixture of 5-10 per cent w/v polyvinyl alcohol, PVA (average MW 50,000-106,000; 98 per cent hydrolysed) and 3 per cent v/v polyethylene glycol 200 (PEG 200), and dried to form the hydrogel film casts. Our in vitro experiments in isotonic phosphate buffer solution (pH 7.4) at 37 degrees C, showed that the release of gentamicin sulphate was dependent on concentration of LBG, and concentration or molecular weight of PVA. With the exception of PVA hydrogel matrix preparations containing 20 per cent w/v LBG, all other formulations showed a significant initial 'burst' release of drug within 6 h. The drug-containing microcapsules in the PVA hydrogel film with 20 per cent w/v LBG, exhibited an almost zero-order release of drug up to 140 h. It is postulated that an effective barrier or high-density membrane enveloping the microcapsules was formed between i-C and LBG because of their unique molecular configurations. This phenomenon, together with the possible adsorption of i-C molecules at the transient oil and outer aqueous phase interface, presumably eliminated the need for a permanent oil phase and/or an O/W surfactant normally required for preparing W/O/W emulsions.

Gentamicin sulfate attachment and release from anodized Ti‐6Al‐4V orthopedic materials

A novel method has been developed to attach, retain, and release antibiotics from titanium based materials. This technique consists of forming porous surface coatings by anodizing and using the surface chemical properties of the oxide coatings to attach antibiotics. Coatings with pores in the size range 0.1-0.5 micron have been formed in acid solutions. The attachment and retainment of gentamicin sulfate, a cationic antibiotic, to the coatings has been investigated using microbiological methods. In vitro test results have shown that the duration of antimicrobial activity on the surface of anodized materials is dependent on the porosity and isoelectric point of the coatings. Using microporous oxide coatings formed in phosphoric acid solutions, it has been found that antimicrobial activity could be retained for more than 2 weeks.

Calcium hydroxyapatite ceramic used as a delivery system for antibiotics.

Porous blocks of calcium hydroxyapatite ceramic were evaluated as delivery systems for the sustained release of antibiotics. We tested gentamicin sulphate, cefoperazone sodium, and flomoxef sodium in powder form placed in a cylindrical cavity in calcium hydroxyapatite blocks, using in vitro studies of elution and in vivo studies in rats. Gentamicin sulphate gave a maximum concentration within the first week, which gradually decreased but was still effective at 12 weeks, when 70% of the antibiotic had been released. Even at this stage the antibiotic concentration from a 75 mg dose was five times the minimum inhibitory concentration for staphylococci. In the in vivo studies the release of gentamicin sulphate into the normal bone of rats was at similar rates and levels. The bacteriocidal activity of the drugs was not affected by packing into calcium hydroxyapatite ceramic and the blocks were completely biocompatible on histology. This new system overcomes the disadvantages of other drug delivery systems, avoiding thermal damage to the antibiotics and a second operation for the removal of the carrier. Some mechanical strength is provided by the ceramic and healing may be accelerated by bone ingrowth into its micropores.