Risperidone Microspheres Research Articles

Development and Characterization of Long-Acting Injectable Risperidone Microspheres Using Biodegradable Polymers: Formulation Optimization and Release Kinetics

Development and Characterization of Long-Acting Injectable Risperidone Microspheres Using Biodegradable Polymers: Formulation Optimization and Release Kinetics

Long-Acting Injectable Antipsychotic Initiation in Child and Adolescent Patients with Psychiatric Disorders.

Objectives: There are currently no long-acting injectable antipsychotics (LAIAs) that are approved by the Food and Drug Administration for use in child and adolescent patients, however these agents are used off-label for the treatment of various psychiatric disorders. This study aims to describe the initiation and maintenance dosing strategies of LAIAs in child and adolescent psychiatry inpatients. Methods: This was a single-site retrospective chart review of patients less than 18 years of age initiated on an LAIA during an acute psychiatric hospitalization between October 1, 2015, and October 31, 2022. Patient demographics and hospital encounter information were collected and analyzed using descriptive statistics. Results: Of the 6402 unique pediatric patients discharged from the acute psychiatric hospital within the specified timeframe, 45 (0.7%) were newly initiated on an LAIA. The average age was 15.6 years (range 10-17), with a greater proportion of male (n = 26, 57.8%) and Black or African American (n = 27, 60%) patients. The LAIA agents prescribed included paliperidone palmitate (n = 21, 46.7%), aripiprazole monohydrate (n = 15, 33.3%), aripiprazole lauroxil (n = 7, 15.6%), haloperidol decanoate (n = 1, 2.2%), and risperidone microspheres (n = 1, 2.2%). Primary diagnosis via International Classification of Diseases-10 code at discharge included schizophrenia spectrum and other psychotic disorders (n = 19, 42.2%); bipolar disorder (n = 14, 31.1%); disruptive, impulse control, and conduct disorders (n = 6, 13.3%); autistic disorder (n = 5, 11.1%); and attention-deficit/hyperactivity disorder (n = 1, 2.2%). Seventeen patients (37.8%) received a loading dose regimen and/or a maintenance dose regimen that differed from adult package-insert dosing. The mean length of stay was 23.7 days, and 14 patients (31.1%) were readmitted to the psychiatric hospital within 6 months of discharge. The mean number of days to readmission was 71.9 days. Conclusions: This retrospective study is the first to focus on LAIA initiation and maintenance dosing strategies of multiple agents in both a child and adolescent patient population. Further research is required to evaluate the impact of LAIAs on clinical outcomes in this patient population.

A Quality By Design (QbD) Prospect in Fabrication of PLGA-based Antipsychotic Long-acting Microspheres: An Alternative to Combination Therapy

Background: Discontinuation and poor compliance with long-term oral medicine are major therapeutic issues in psychosis treatment. Poorer long-term outcomes may result from non-compliance as well as a higher chance of relapse. In order to sustain therapeutic drug plasma levels, co-administration of oral antipsychotics is necessary for commercially available longacting injections of second-generation antipsychotics, as they have a lag period of approximately three weeks during the drug release process. Methods: Poly(lactic-co-glycolic acid) (PLGA) encapsulated microspheres loaded with risperidone were fabricated in the current research for intramuscular administration. The single emulsion solvent evaporation technique was applied for the fabrication of microspheres. Risperidone microspheres were prepared using PLGA grade 75:25. Particle size, drug content and entrapment efficiency with a central composite design were the main optimization parameters for the formulation. The microspheres were characterized by different techniques, namely Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffractometry (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The drug content, entrapment efficiency, morphology, particle size, and in vitro release profiles, along with release kinetics of the risperidone microspheres, were studied. Results and Discussion: The microspheres produced by the single emulsion solvent evaporation approach show smooth and spherical morphology, with particle size ranging from 3 μm to 6 μm, drug content of 99.7%, and entrapment efficiency of 98.2% with little burst release of 3% to 10%, providing drug release for 45 days and exhibiting zero order release kinetics and Korsmeyer- Peppas model for non-fickian drug release from the polymeric matrix. By applying the Quality by Design (QbD) approach and formulation parameters, microspheres with appropriate particle size, morphology, enhanced drug content, entrapment efficiency and desirable drug release profile for depot formulation can be obtained successfully. Conclusion: The optimized microspheres, in comparison to the marketed Risperdal Consta™, show enhanced potential for a better depot formulation, which can further improve patient compliance.

Biorelevant in vitro drug release conditions ameliorate in-vitro-in-vivo relationship of parenteral risperidone microspheres

Biorelevant in vitro drug release conditions ameliorate in-vitro-in-vivo relationship of parenteral risperidone microspheres

Assessment of risk factors of treatment discontinuation among patients on paliperidone palmitate and risperidone microspheres in France, Germany and Belgium

BackgroundLong-acting antipsychotics (e.g. 1-monthly (PP1M) / 3-monthly (PP3M) injection forms of paliperidone palmitate) have been developed to improve treatment continuation in schizophrenia patients. We aim to assess risk factors of treatment discontinuation of patients on paliperidone palmitate and risperidone microsphere. Additionally, treatment discontinuation between patients with PP1M and PP3M was compared.MethodsThe IQVIA Longitudinal Prescription databases were used. Risk factors of treatment discontinuation were identified by a multilevel survival regression using Cox proportional hazards model. Kaplan Meier analyses were performed by identified significant risk factors.ResultsTwenty-five thousand three hundred sixty-one patients (France: 9,720; Germany: 14,461; Belgium: 1,180) were included. Over a one-year follow-up period, a significant lower treatment discontinuation was observed for patients newly initiated on paliperidone palmitate (53.8%) than those on risperidone microspheres (85.4%). Additionally, a significantly lower treatment discontinuation was found for ‘stable’ PP3M patients (19.2%) than ‘stable’ PP1M patients (37.1%). Patients were more likely to discontinue when drugs were prescribed by GP only (HR = 1.68, p < 0.001 vs. psychiatrist only) or if they were female (HR = 1.07, p < 0.001), whereas discontinuation decreased with age (31–50 years: HR = 0.95, p = 0.006 and > 50 years: HR = 0.91, p < 0.001 vs. 18–30 years).ConclusionsThis study demonstrates that patients stay significantly longer on treatment when initiated on paliperidone palmitate as compared to risperidone microspheres. It also indicated a higher treatment continuation of PP3M over PP1M. Treatment continuation is likely to be improved by empowering GPs with mental health knowledge and managing patients by a collaborative primary care-mental health model. Further research is needed to understand why females and younger patients have more treatment discontinuation.

Assessing Outcomes Between Risperidone Microspheres and Paliperidone Palmitate Long-Acting Injectable Antipsychotics Among Veterans.

Long-acting injectable antipsychotics (LAIAs) are integral for managing schizophrenia, schizoaffective disorder, and bipolar I disorder among veterans. Studies comparing LAIAs, such as risperidone microspheres and paliperidone palmitate, are limited. The primary objective of our study was to compare the number of psychiatric hospitalizations among veterans initiated on risperidone microspheres and those taking paliperidone palmitate pre- and post-LAIA initiation. We included veterans who had received ≥ 2 injections of risperidone microspheres or paliperidone palmitate between January 1, 2016 and December 31, 2018. Nonadherence was defined as missing an injection by > 3 days for risperidone microspheres and > 7 days for paliperidone palmitate. Pre-LAIA and post-LAIA hospitalizations and rehospitalizations were assessed using a pre-post design with equivalent periods. Descriptive statistics were used for demographics and diagnoses. Nonparametric tests were used to analyze primary and secondary outcomes. The study included 97 veterans; 44 took risperidone microspheres and 53 received paliperidone palmitate. Participants' average mean (SD) age was 46 (13.8) years, 92% were male, and 94% were diagnosed with schizophrenia or schizoaffective disorder. Veterans administered risperidone microspheres had fewer mean (SD) post-LAIA hospitalizations (0.4 [1.0] vs 0.9 [1.5]; P = .02), were less likely to be rehospitalized (22.7% vs 47.2%; P = .013) and had a shorter mean (SD) treatment duration (41.6 [40.2] vs 58.2 [45.7] weeks; P = .04) compared with paliperidone palmitate. Veterans receiving risperidone microspheres had fewer posttreatment psychiatric hospitalizations and were less likely to be rehospitalized.

Effect of polymer source variation on the properties and performance of risperidone microspheres

Owing to their inherent heterogeneity, determination of similarity of poly (lactic-co-glycolic acid) (PLGA) polymers is very challenging. The complexity in controlling PLGA characteristics has been recognized as an obstacle to the development of PLGA based long-acting complex drug products (such as microspheres). The objectives of the present study were: (1) to determine minor differences in the physicochemical characteristics (such as inherent viscosity, molecular weight (Mw), monomer ratio (L/G ratio), glass transition temperature (Tg), and blockiness) as well as in the hydrolytic degradation profiles of PLGAs from different sources; and (2) to investigate the impact of PLGAs from different sources on the properties and in vitro performance of risperidone microspheres. Four PLGA polymers were purchased from different sources with similar inherent viscosity and/or Mw, L/G ratio and end groups as per the manufacturers’ certificate of analysis (CoA). The physicochemical properties of these PLGAs were characterized using the same in-house methods and exhibited differences in inherent viscosity, Mw, blockiness and residue amount. Risperidone was chosen as the model drug and four microsphere formulations were prepared via the same solvent extraction/evaporation method using the PLGAs from different sources. The critical quality attributes of the microspheres (such as particle size, porosity and average pore diameter) and their in vitro release characteristics (burst effect and release rate) were shown to be different. A strong linear correlation was established between risperidone release and PLGA blockiness. This is the first time that such a correlation has been established, which promotes the potential need to further investigate the impact of PLGA blockiness on other PLGA based controlled release drug products.

PMH46 Treatment Patterns With Aripiprazole Lauroxil Versus Other Atypical Long-Acting Injectable Antipsychotics in Patients With Schizophrenia: A Retrospective Electronic Health Records Database Study

To describe treatment patterns among patients with schizophrenia initiating treatment with aripiprazole lauroxil (AL) versus other atypical long-acting injectable (aLAI) antipsychotics (paliperidone palmitate [PP], aripiprazole monohydrate [AM], risperidone microspheres [RIS]) using a unique web-based electronic health record (EHR) system available free to single-provider and small group outpatient practices across the US. Adults (≥18 years) with schizophrenia who had ≥1 aLAI prescription between 10/2015 and 10/2017 and continuous data for 6 months before and 12 months after initial (index) aLAI prescription were identified retrospectively. Post-index outcomes included index aLAI discontinuation, persistence, adherence (proportion of index aLAI days covered [PDC]), switching, and re-initiation. Adjusted odds ratios (ORs) were calculated using AL as the referent. Mean (SD) patient age was 45.9 (15.1) years (N=1730) and 64% of patients were male. Index treatments included AL (n=159), PP (n=954), AM (n=306), and RIS (n=311). Overall, 84% discontinued their index aLAI; adjusted ORs (95% CIs) relative to AL were 0.77 (0.48-1.25; PP), 0.67 (0.39-1.14; AM), and 2.72 (1.40-5.30; RIS). Median times to discontinuation of index aLAI were 90 (AL), 33 (PP), 85 (AM), and 14 (RIS) days. Median PDCs were 24% (AL), 8% (PP), 16% (AM), and 4% (RIS). Overall, 29% of patients switched from their index aLAI; adjusted ORs vs AL for switching were 0.89 (0.59-1.35; PP), 0.44 (0.31-0.63; AM), and 0.86 (0.64-1.17; RIS). Among patients who discontinued their index aLAI, 21% re-initiated (AL, 30%; PP, 19%; AM, 15%; RIS, 26%). Adjusted ORs vs AL for re-initiation of index aLAI were 0.62 (0.40-0.95; PP), 0.45 (0.27-0.76; AM), and 0.95 (0.59-1.53; RIS). In this real-world EHR database study, AL treatment was associated with a lower rate of discontinuation, greater persistence, and better adherence (based on PDC) versus RIS, whereas outcomes were generally comparable between AL and AM or PP groups.

Assessment of risk factors of treatment discontinuation among patients on paliperidone palmitate and risperidone microspheres in france, germany and belgium – a retrospective database study

IntroductionLong-acting antipsychotics (e.g. 1-monthly (PP1M) / 3-monthly (PP3M) injection forms of paliperidone palmitate) have been developed to improve treatment continuation in schizophrenia patients.ObjectivesTo assess risk factors of treatment discontinuation in patients on paliperidone palmitate and risperidone microsphere. Additionally, treatment continuation between patients with PP1M and PP3M was compared.MethodsThe IQVIA Longitudinal Prescription databases were used. Risk factors of treatment discontinuation were identified by a multilevel survival regression using Cox proportional hazards model. Kaplan Meier analyses were performed by identified significant risk factors.Results25,361 patients (France: 9,720; Germany: 14,461; Belgium: 1,180) were included. Over a one-year follow-up period, a significant higher treatment continuation was observed for patients newly initiated on paliperidone palmitate (46.2%) than those initiated on risperidone microspheres (14.6%). Additionally, a significantly higher treatment continuation was found for ‘stable’ PP3M patients (81.8%) than ‘stable’ PP1M patients (62.9%). Patients were more likely to discontinue when drugs prescribed by GP only (HR = 1.68, p &lt; 0.001 vs. psychiatrist only) or being females (HR = 1.07, p &lt; 0.001), whereas discontinuation rate decreased with age (31-50 years: HR = 0.95, p = 0.006 and &gt; 50 years: HR = 0.91, p &lt; 0.001 vs. 18-30 years).ConclusionsPaliperidone palmitate was associated with a significantly higher treatment continuation than risperidone microspheres. Treatment continuation is likely to be improved by targeting young patients (18-30 years), empowering GPs with mental health knowledge and managing patients by a collaborative primary care-mental health model. Further research is needed to understand why females have more treatment discontinuation.DisclosureRui Cai, Flore Decuypere and Pierre Chevalier are IQVIA employees and served as paid consultants to Janssen during the conduct of this study. Antonie Wimmer, Pascal Guillon, Stefan Pype, Annabelle Godet, Valeria Timtschenko are Janssen employees.

Plasma Levels of Long-Acting Injectable Antipsychotics in Outpatient Care: A Retrospective Analysis.

PurposeAntipsychotic efficacy in schizophrenia depends on its availability in the body. Although therapeutic outcomes remain still far from satisfactory, therapeutic drug monitoring is not a common part of clinical practice during treatment with long-acting injectable antipsychotics (LAI AP). The real effectiveness of LAI AP is thus uncertain.Patients and MethodsWe made a retrospective evaluation of plasma levels of LAI AP. Collection of blood samples was performed just before the drug application and one week later. Forty patients with a stabilized clinical condition and steady-state plasma levels were included.ResultsIn the observed cohort of patients, flupentixol decanoate (n = 23) was the most often used drug, followed by fluphenazine decanoate (n = 7), haloperidol decanoate (n = 5), paliperidone palmitate (n = 3), and risperidone microspheres (n = 2). Just 5 of 40 patients were treated with a monotherapy. In the period before the application, 60% of the patients did not reach the therapeutic reference range (TRR) and 20% of the patients had an undetectable plasma level. At the time of collection of the second blood samples performed after 7 days, 24% of the patients were under the TRR.ConclusionWe have found a surprisingly high incidence of plasma levels under the TRR in patients treated with LAI AP. Notwithstanding individual variability in pharmacokinetics, it seems that LAI AP may be underdosed in usual clinical practice.

Long-acting injectable antipsychotics: what, when, and how

Current guidelines for the treatment of patients with schizophrenia advocate that patients receive treatment with a long-acting injectable (LAI) antipsychotic medication if they prefer such treatment or if they have a history of poor or uncertain adherence. Available LAI formulations in the United States include first-generation antipsychotics (fluphenazine decanoate and haloperidol decanoate), risperidone/paliperidone containing products (risperidone microspheres, paliperidone palmitate, and risperidone subcutaneous), aripiprazole containing products (aripiprazole monohydrate and aripiprazole lauroxil), and olanzapine pamoate. LAI antipsychotics can address the guesswork about adherence status and patients may prefer them if they are offered this as a choice, including individuals early in their disease course. Additional approved indications in the United States for LAI antipsychotics include bipolar I disorder maintenance treatment for risperidone microspheres and aripiprazole monohydrate, and schizoaffective disorder for paliperidone palmitate once monthly. Differences and similarities among the different products are discussed, including guidance regarding optimal treatment selection. Tips are provided to enhance effective patient communication to maximize the likelihood of acceptance of this treatment modality.

Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview.

The availability of long-acting injectable (LAI) antipsychotics for the treatment of schizophrenia provides clinicians with options that deliver continuous drug exposure and may improve adherence compared with daily oral antipsychotics. However, all LAI antipsychotics have unique formulations and pharmacokinetic characteristics that have implications for medication selection, administration interval, and injection site. This review outlines key differences in drug formulations and pharmacokinetics among LAI antipsychotics. A systematic search of the PubMed database was conducted to identify physical and formulation properties and pharmacokinetic data of commercially available LAI antipsychotics, including flupentixol decanoate, fluphenazine decanoate, haloperidol decanoate, zuclopenthixol decanoate, aripiprazole monohydrate, aripiprazole lauroxil, olanzapine pamoate, paliperidone palmitate, risperidone microspheres, and risperidone polymeric microspheres. Additional information was obtained from package inserts and product monographs. Relevant data on drug properties, administration details, pharmacokinetic parameters, and oral dose equivalencies of LAI antipsychotics are summarized. Based on our analysis, formulation characteristics (e.g., vehicle medium) and administration characteristics (e.g., injection site) can affect rate of absorption and adverse effects and may factor into whether oral supplementation or an additional injection is needed. Dose adjustments may be necessary based on potential drug–drug interactions, and approximate dose equivalence with oral formulations can help inform titration when switching from oral to LAI formulations. Clinicians administering LAI antipsychotics should consider these formulation and pharmacokinetic factors to maximize clinical impact and to adjust to an individual patient’s needs and treatment goals.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40263-020-00779-5.

New product intros (coblopasvir dihydrochloride, dasiglucagon, 2-deoxyglucose, estetrol/drospirenone (new combination), risperidone microspheres (new formulation), SaNOtize nitric oxide nasal spray (NONS), tocilizumab (new indication))

New product intros (coblopasvir dihydrochloride, dasiglucagon, 2-deoxyglucose, estetrol/drospirenone (new combination), risperidone microspheres (new formulation), SaNOtize nitric oxide nasal spray (NONS), tocilizumab (new indication))

In vitro-in vivo correlation of parenteral PLGA microspheres: Effect of variable burst release

Development of IVIVCs is a very complicated process, especially for complex drug products such as parenteral PLGA microspheres with multiphasic drug release characteristics. Specifically, microspheres that exhibit an initial burst release phase are even more challenging since the in vitro and in vivo burst release phases may not be comparable if drug absorption is rate-limiting at this stage. Therefore, the objectives of the present work were: 1) to investigate the predictability of developed IVIVCs for the in vivo burst release phase based on the in vitro burst release phase of the formulations; and 2) to evaluate the impact of variable burst release on the predictability of the developed IVIVCs for two different types of microsphere-based drug products. Accordingly, Risperdal Consta® (Risperidone) and Lupron Depot® (Leuprolide acetate, LA) were selected as model products. Compositionally equivalent risperidone and LA formulations with variable burst release phases were prepared with manufacturing process changes (such as solvent systems and mixing methods). The prepared microspheres exhibited differences in critical physicochemical properties (such as particle size, porosity, average pore diameter, and drug distribution) and hence differences in their in vitro release characteristics (such as variable burst release and release rate). The in vitro and in vivo (rabbit model (intramuscular injection) burst release were similar for the risperidone microspheres but were significantly different for the LA microspheres. This had an impact on the complexity of the developed IVIVC models. Level A IVIVCs with the ability to predict various types of burst release were developed using time scaling and shifting factors. Moreover, it was observed that IVIVCs developed using formulations with less variation in burst release had better predictability and vice-versa. Thus, the present research has provided a comprehensive understanding of the impact of the burst release phase on the development, complexity, and predictability of IVIVCs for complex parenteral microspheres containing a variety of therapeutic molecules.

Real-life persistence of long-acting injectable antipsychotics in schizophrenic patients: Aretrospective observational study in France .

Antipsychotics exhibit different profiles of efficacy and safety in patients with schizophrenia. It has recently been reported that the risk of rehospitalization was the lowest with paliperidone palmitate (PP), a long-acting injectable (LAI), when compared with other LAIs (of zuclopenthixol, perphenazine, and olanzapine). We aimed to investigate whether treating patients with PP was also associated with improved real-life treatment persistence. We conducted a retrospective observational study of the LAI antipsychotics (LAIAs) dispensed in French retail pharmacies. Treatment persistence was defined as the non-discontinuation of LAIAs for ≥5 months after LAIA initiation (and was also analyzed by Kaplan-Meier persistence curves). A total of 4,492 patients were included in the study. The persistence rate was significantly greater for LAI-PP (64.5%) than for either LAI haloperidol decanoate (HD) or LAI risperidone microspheres (R) (46.4% and 35.4%, respectively). Multivariate Cox analyses illustrated that LAIA initiation with HD or R significantly increased the risk of discontinuation when compared with PP. PP demonstrated a significantly higher persistence rate than HD or R. Moreover, LAIA initiation with HD or R significantly increased the risk of treatment discontinuation relative to PP. Further comparative studies are required to comprehensively determine whether PP has a better efficacy and/or safety profile than other LAIs.

Sustained-Release Risperidone via Subcutaneous Injection: A Systematic Review of RBP-7000 (PERSERIS™) for the Treatment of Schizophrenia.

RBP-7000 (PERSERIS™) is a once-monthly subcutaneously administered formulation of risperidone that does not require oral supplementation when initiated. As with risperidone microspheres, RBP-7000 is required to be stored in a refrigerator. The injection kit, consisting of two syringes (one containing liquid polymer, the other containing risperidone powder), will need to come to room temperature prior to mixing their contents. RBP-7000 is administered in the abdomen using an 18 G 5/8-inch length needle. In an 8-week Phase 3 study in patients with acute schizophrenia, monthly RBP-7000 at doses of 90 mg (equivalent to oral risperidone 3 mg/day) and 120 mg (equivalent to oral risperidone 4 mg/day) were superior to placebo on changes in the PANSS total score. Overall tolerability was consistent with what is already known about risperidone/paliperidone, and the most common adverse reactions (≥5% and greater than twice placebo) were increased weight, sedation/somnolence, and musculoskeletal pain. Mean subject-reported injection site pain Visual Analog Scale scores (0=no pain to 100=unbearably painful) were similar for all treatment groups following both injections; with pain scores decreasing from a mean of 27 at 1 minute after the first dose to a range of 3 to 7 at 30 to 60 minutes postdose. RBP-7000 represents the first second-generation antipsychotic to be available as a subcutaneously administered long-acting injectable; having different choices of formulations can make the difference in finding the right intervention for the right patient.

Extent of use of long-acting injectable antipsychotics in children and adolescents within Indiana Medicaid.

Introduction:Oral formulations of the antipsychotics aripiprazole, asenapine, lurasidone, olanzapine, paliperidone, quetiapine, and risperidone are indicated for use in pediatrics for several diagnoses. Long-acting injectable (LAI) antipsychotics are of interest in this special population because they may be used due to convenience and desire to improve adherence, despite limited support in the literature. The primary intent of this study is to provide descriptive information on the use of paliperidone palmitate, risperidone microspheres, aripiprazole extended-release injection, and olanzapine pamoate in pediatric patients within Indiana Medicaid.Methods:This study was a retrospective database analysis, which retrieved information from Indiana Medicaid over a 2-year timeframe spanning from July 1, 2012, through June 30, 2014. The study included the prescription medications filled for all children and adolescents within Indiana Medicaid who received the LAI antipsychotics paliperidone palmitate, risperidone microspheres, aripiprazole extended-release injection, and olanzapine pamoate.Results:From July 1, 2012, through June 30, 2014, 150 Indiana Medicaid patients younger than 18 years old were prescribed a LAI atypical antipsychotic. A total of 1013 LAI atypical antipsychotic doses were billed to Indiana Medicaid during the study period for pediatric patients. Paliperidone palmitate was billed most frequently.Discussion:Long-acting injectable atypical antipsychotics are being prescribed for children and adolescents within Indiana Medicaid, despite minimal clinical evidence supporting use. There is a need for further research in this area to increase generalizability of results and aid in implementation of policies to prevent inappropriate use of LAI antipsychotics in children and adolescents.

Long Term Efficacy of the Treatment with Olanzapine Pamoate, Risperidone and Aripiprazole Monohydrate

The use of long-acting injectable antipsychotics (LAIs) is considered to be an important treatment option, especially in early stages of schizophrenia. The aim of this study was to evaluate the efficacy, safety and sustained remission in schizophrenia patients treated with three of the available LAIs substances: olanzapine pamoate, risperidone microspheres and aripiprazole monohydrate. A retrospective chart review study evaluating the efficacy of LAIs compared to oral antispychotics during a five years period was performed. Of the 102 patients included in the study, 52 (50.9%) continued LAIs: olanzapine pamoate (n = 20, 38.4%), risperidone microsphere (n = 22, 42.3%), aripiprazole monohydrate (n = 10, 19.3%). In the LAIs group the number of relapses was smaller than in the oral antipsychotics group (12 vs. 23, P [ 0.05) as well as the number of admissions (15 vs. 30, P [ 0.05). In conclusion, relapse in schizophrenia is strongly related to nonadherence. LAIs prescription overall was underutilized despite their efficacy. Future randomized studies are needed to evaluate the long term efficacy of LAIs compared to oral treatment.

An Accelerated Release Method of Risperidone Loaded PLGA Microspheres with Good IVIVC.

A long release period lasting several days or several weeks is always needed and thereby it is tedious and time consuming to screen formulations of such microspheres with so long release period and evaluate their release profiles in vitro with conventional long-term or "real-time" release method. So, an accelerated release testing of such system is necessary for formulation design as well as quality control purpose. The purpose of this study is to obtain an accelerated release method of risperidone loaded poly(lactic-co-glycolic acid) (PLGA) microspheres with good in vitro/in vivo correlation (IVIVC). Two formulations of risperidone loaded PLGA microspheres used for evaluating IVIVC were prepared by O/W method. The accelerated release condition was optimized by investigating the effect of pH, osmotic pressure, temperature and ethanol concentration on the release of risperidone from microspheres and the in vitro accelerated release profiles of risperidone from PLGA microspheres were obtained under this optimized accelerated release condition. The plasma concentration of risperidone were also detected after subcutaneous injection of risperidone loaded microspheres to rats. The in vivo cumulative absorption profiles were then calculated using Wagner-Nelson model, Loo- Riegelman model and numerical convolution model, respectively. The correlation between in vitro accelerated release and in vivo cumulative absorption were finally evaluated with Least Square Method. It was shown that temperature and ethanol concentration significantly affected the release of risperidone from the microspheres while pH and osmotic pressure of release media slightly affected the release behavior of risperidone. The in vitro release of risperidone from microspheres were finally undergone in PBS (pH7.0, 300mosm) with 20% (V/V) ethanol at 45°C. The sustained and complete release of risperidone was observed in both formulations under the accelerated release condition although these two release profiles were dissimilar. The correlation coefficients (R2) of IVIVC were all above 0.95 and the slopes were all between 0.9564 and 1.1868 in spite of fitted model and microsphere formulation. An in vitro accelerated release method of risperidone microspheres with good IVIVC was established in this paper and this accelerated release method was supposed to have great potential in both in vivo performance prediction and quality control for risperidone loaded PLGA microspheres.

Influence of CYP2D6 genotypes on the pharmacokinetics and treatment effect of risperidone in patients using extended-release risperidone microspheres for intramuscular injection

Influence of CYP2D6 genotypes on the pharmacokinetics and treatment effect of risperidone in patients using extended-release risperidone microspheres for intramuscular injection