Long-acting Injectable Drug Research Articles

Clinical experience with the long-acting injectable formulation of the atypical antipsychotic, risperidone

SUMMARYBackground: To detail specific effects of long-acting risperidone on individuals with schizophrenia and their way of life in a series of four cases.Method: Four patients with schizophrenia were selected from four different psychiatric centres. Patients were established on an oral dose of risperidone (1-4 mg/day) for 2 weeks. Based on their oral dose, they then received intramuscular injections of 25 mg or 50 mg of long-acting risperidone every 2 weeks, which could be adjusted according to clinical response. Assessments of efficacy (Positive And Negative Syndrome Scale, Clinical Global Impression-Severity) and safety (Extrapyramidal Symptom Rating Scale) were made at intervals throughout a 1 -year period.Results: Patients demonstrated a variety of reasons for receiving a long-acting injectable antipsychotic drug, including insufficient control of symptoms, adverse events and convenience. After 1 year of treatment with long-acting risperidone, all patients showed improvements in their symptoms of schizophrenia over their original stable condition, and benefited from a considerable reduction or total disappearance of pre-existing extrapyramidal symptoms. Patients were more socially interactive, with no signs of sedation, fatigue, confusion, depression or anxiety, and none were considered to have relapsed or to require hospitalisation. Three of the four patients were considered to have had no signs of illness after 1 year, one of whom had returned to college and another to work. They demonstrate that patients can be switched from oral and depot medications without problems. There was little pain or discomfort and no inflammatory response experienced at the injection site.Conclusion: The cases demonstrate the suitability of long-acting risperidone in patients benefiting from long-term treatment and suggest its potential in all patients who are at risk of relapse.

In vivo biocompatibility and degradability of a novel injectable-chitosan-based implant

A novel injectable-chitosan-based delivery system with low cytotoxicity was fabricated in the study. The chitosan microspheres with small particle size, low crystallinity and good sphericity were prepared by a spray-drying method followed by treating with a crosslinker. In the study, a naturally occurring crosslinking reagent (genipin), which has been used in herbal medicine and in the production of food dyes, was used to crosslink the chitosan microspheres. The glutaraldehyde-crosslinked counterparts were used as a control. Histological study of the genipin-crosslinked chitosan microspheres injected intramuscularly into the skeletal muscle of a rat model showed a less inflammatory reaction than its glutaraldehyde-crosslinked counterparts. The results of the scanning electron microscopic examination indicated that the glutaraldehyde-crosslinked chitosan microspheres retrieved at 12-week postoperatively were already degraded into a loose and porous structure. However, the degradation of the genipin-crosslinked chitosan microspheres was not significant after 20 weeks of implantation. The results of the study demonstrated that the genipin-crosslinked chitosan microspheres have a superior biocompatibility and a slower degradation rate than the glutaraldehyde-crosslinked chitosan microspheres. Accordingly, the genipin-crosslinked chitosan microspheres may be a suitable polymeric carrier for long-acting injectable drug delivery.

A potent peptidomimetic inhibitor of HSV ribonucleotide reductase with antiviral activity in vivo: R. Déziel, N. Moss, M. Liuzzi, P. Beaulieu, A.-M. Bonneau, C. Bousquet, M. Llinas-Brunet, J. G. Chafouleas, J.-S. Duceppe, J.-M. Ferland, M. Garneau, J. Gauthier, E. Ghiro, S. Goulet, L. Grenier, J. Jaramillo, R.L. Krogsrud, L. Lagacé, R. McCollum, S. Nawoot, R. Plante, D. Wernic, and Y.

The design and synthesis of novel HIV-1 protease inhibitors (PIs) (1–22), which display high potency against HIV-1 wild-type and multi-PI-resistant HIV-mutant clinical isolates, is described. Lead optimization was initiated from compound 1, a Phe–Phe hydroxyethylene peptidomimetic PI, and was directed towards the discovery of new PIs suitable for a long-acting (LA) injectable drug application. Introducing a heterocyclic 6-methoxy-3-pyridinyl or a 6-(dimethylamino)-3-pyridinyl moiety (R3) at the para-position of the P1′ benzyl fragment generated compounds with antiviral potency in the low single digit nanomolar range. Halogenation or alkylation of the metabolic hot spots on the various aromatic rings resulted in PIs with high stability against degradation in human liver microsomes and low plasma clearance in rats. Replacing the chromanolamine moiety (R1) in the P2 protease binding site by a cyclopentanolamine or a cyclohexanolamine derivative provided a series of high clearance PIs (16–22) with EC50s on wild-type HIV-1 in the range of 0.8–1.8 nM. PIs 18 and 22, formulated as nanosuspensions, showed gradual but sustained and complete release from the injection site over two months in rats, and were therefore identified as interesting candidates for a LA injectable drug application for treating HIV/AIDS.