Formulation

Basic composition of the implant is approximately 50% naltrexone, 49% of biodegradable polylactic based polymer and £1% magnesium stearate.  The polymer material is similar material to that used in biodegradable sutures and screws and is an FDA approved substance. The polymer has been used previously in implantable norethisterone formulations (Beck et al, 1981). The incidence of foreign body reactions with polylactide biodegradable polymers has been recently reviewed (Perrin et al., 1997). The authors estimated an incidence of foreign body reaction of 4.9%, from accumulated data from 412 patients.

Manufacturing and Sterility

The implants are manufactured with assistance from Go Medical Industries Pty Ltd. Go Medical is a medical devices manufacturer with ISO 9001 and EN 46001 certification, TGA (Australia) and FDA approved medical devices manufacturing facility and is also authorised to use the CE Mark on its medical devices only. 

Implants are sterilised with gamma radiation between a minimum of 25kGy and no more than 40kGy.  Regular crushed bioburden tests are also conducted on samples from each batch.

Packaging

Each implant (i.e., one syringe) contains 10 pellets.  Each pellet is 8 mm in diameter and 5 mm high and weighs approximately 0.3 g but contains approximately 0.15 g of naltrexone.  Therefore, each syringe contains in total, approximately 3.0 g of pellets which is equivalent to 1.5 g of naltrexone.

The recommended dosage is for two implants (i.e., two syringes) releasing rate at 0.4% of its naltrexone mass per day to be initially implanted subcutaneously.  Therefore initial procedure will see the patient implanted with 3.0 g of naltrexone in total.  Re-implant is recommended at six months or if regular monitoring of free naltrexone levels in blood serum falls below 2 ng/ml.

In-vitro dissolution data

In-vitro dissolution experiments were conducted with a standard method.  One  naltrexone-loaded polymer tablet was placed in 100 mL,  0.02 M phosphate buffer solution at pH 7.4., maintained at 37°C.  Samples were collected daily from the release medium and the entire release medium was replaced daily with fresh buffer.   The amount of released naltrexone in solution was quantified by an UV spectrophotometer at 281 nm.  Results for representative batches of the implantable formulation are shown in Fig.1.