Aripiprazole Lauroxil NanoCrystal^®Dispersion Technology (Aristada Initio^®)

Abstract

Nonadherence to antipsychotic medications for the treatment of schizophrenia is a widely recognized concern, leading to poorer clinical outcomes and higher treatment costs. Long-acting injectable (LAI) antipsychotics offer an extended dosing interval option for patients, although the current options may require an oral overlap at initiation. Aripiprazole lauroxil is an LAI that offers multiple dosing options but requires oral treatment overlap during initiation for the first 21 consecutive days. As an alternative to oral overlap, a novel nano-crystalline milled dispersion delivery system of aripiprazole lauroxil was recently approved as a one-day regimen to be added to aripiprazole lauroxil treatment.

Size matters: the importance of particle size in a newly developed injectable formulation for the treatment of schizophrenia

“…The newly developed formulation is a NanoCrystal Dispersion of AL (Aristada Initio ® ), which contains the same prodrug that is in AL, but with nanometer-sized particles instead of micrometer-sized particles. 7 A comparison of the original AL formulation with the new AL NCD formulation is presented in Table 1. The smaller particle size of AL NCD results in faster dissolution of the drug than with AL, and administration of AL NCD was therefore expected to be associated with an earlier rise in plasma aripiprazole levels than with AL.…”

“…21 Prior to the approval of AL NCD , the only option for initiation of AL therapy was to prescribe 21 days of concomitant oral aripiprazole to provide relevant plasma levels during the slow dissolution of the AL dose. 7 The availability of two options for initiating AL therapy, each offering different advantages, allows the clinician to choose the regimen best suited to the individual patient ( Table 2). The 21-day oral supplementation regimen for AL initiation requires one fewer injection than does the 1-day AL initiation regimen; the 1-day initiation regimen, however, can be administered by the clinician in a single office visit.…”

“…6 The AL formulation is an injectable suspension of micrometer-sized particles designed for slow dissolution (Figure 1). 7 The rate of dissolution, or release of the drug from the particles, allows for a dosing interval of up to 2 months. 8 But the same slow-release attribute of AL also means that it takes between 6 and 7 weeks for aripiprazole to reach peak plasma levels.…”

“…The clinical goal for embarking on this strategy was to reduce the time needed for oral supplementation to a single-day initiation of AL while providing plasma levels of aripiprazole that were comparable to those observed with the 21-day oral aripiprazole initiation regimen. 7 To that end, a more rapidly dissolving formulation of AL, known as Aripiprazole Lauroxil NanoCrystal ® Dispersion (AL NCD ), was developed that requires only a 1-day oral aripiprazole initiation regimen.…”

Quality by Design (QbD) Approach for Optimization and Characterization of Micro emulsion based Nasal formulation of Antipsychotic/Antischizophrenic Drug-Aripiprazole

“…Aripiprazole is an atypical antipsychotic drug with chemical name 7-[4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy]-3,4-dihydro-2(1H) quinolinone. 1 It belongs to the chemical class of benzisoxazole derivatives and is indicated for the management of schizophrenia. Study revealed that Aripiprazole have high affinity towards D2, D3 -Dopamine and 5 -HT 7 serotonin receptors.…”