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.

The focus of present work was to prepare salt of aripiprazole (APZ) with dicarboxylic acids to improve physicochemical properties the drug. Dicarboxylic acids used in the study were malonic acid, maleic acid and succinic acid. The salts were prepared with solubilization-crystallization method. The salts were characterized for pH-solubility, dissolution, and stabilities. The Fourier infrared spectroscopy, X-ray powder diffraction, differential scanning calorimetry and near infrared chemical imaging indicated formation of new solid phase. pH-solubility profiles of the salts were similar to the drug except higher solubility were observed in the salts at all tested pH. The highest solubility was observed for APZ-Malonate salt among all the prepared salts. The solubility curve was inverted ‘V’ shape for APZ-maleate and APZ-succinate while it was inverted ‘U’ shape for APZ-malonate. The water solubility of APZ, APZ-malonate, APZ-maleate and APZ-succinate were 0.07 ± 0.02, 3503.9 ± 37.4, 269.3 ± 6.9 and 729.4 ± 9.4 µg/mL, respectively. The dissolution was 2.9 ± 0.4, 18.4 ± 3.9, 19.5 ± 1.4 and 36.6 ± 4.0% in 45 min for APZ, APZ-maleate, APZ-malonate, and APZ-succinate. The stabilities of the salts were similar to the drug. Thus, salts improved the physicochemical properties of the drug, and have similar stability profiles as that of APZ.

We recently reported that aripiprazole (ARP), an antipsychotic drug, binds strongly to human serum albumin (HSA), the major drug binding protein in serum. It is known that uremic toxins that accumulate during renal disease affect the interaction between HSA and drug binding. In this study, the issue of how uremic toxins (indoxyl sulfate, indole acetic acid and p-cresyl sulfate) affect the binding of ARP to HSA was investigated. Equilibrium dialysis experiments revealed that all uremic toxins inhibited the binding of ARP to HSA although the inhibitory effects differed, depending on the specific uremic toxin. The potency of inhibition can be partially explained by the affinities of uremic toxins to HSA. Fluorescence displacement experiments suggested that ARP as well as all uremic toxins bind to site II of HSA. The inhibitory effects of the toxins on the binding of ARP for the drugs binding to the diazepam subsite are significantly larger, comparing with those for binding to arylpropionic acids subsite. Interestingly, induced circular dichroism (CD) spectra indicated that the spatial orientation of p-cresyl sulfate in the binding pocket is different from that for indoxyl sulfate and indole acetic acid. The limited findings obtained herein are important data in considering the effects of uremic toxins on the pharmacokinetics of ARP and the drugs that bind to site II on HSA, particularly drugs binding to diazepam binding site in site II.

The last step of cholesterol biosynthesis is the conversion of 7-dehydrocholesterol (7-DHC) into cholesterol, a reaction catalyzed by dehydrocholesterol reductase 7 (DHCR7). Investigation of the effect of Dhcr7 single-allele mutations on the metabolism of aripiprazole (ARI) and cariprazine (CAR) in maternally exposed transgenic pups revealed that ARI, CAR, and their active metabolites were decreased in the liver and brain of Dhcr7+/–. This difference in the drug and metabolite levels resulted in an increased turnover of ARI and CAR in tissues from Dhcr7+/– animals, indicating an enhanced metabolism, which was at least partially due to increased levels of Cyp2d6 in the liver of Dhcr7+/– mice. Finally, experiments with both WT and DHCR7+/– human fibroblasts revealed lower drug levels in DHCR7+/– heterozygous cells. Our findings have potential clinical implications, as DHCR7 heterozygosity is present in 1–3% in the human population, and these individuals might have reduced therapeutic levels of Cyp2d6-metabolized medications and are putatively more susceptible to unwanted side effects.

PurposeWe developed and validated an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneous therapeutic drug monitoring (TDM) and clinical pharmacokinetic antipsychotic drugs: clozapine (CLP), chlorpromazine (CPZ), risperidone (RPD), paliperidone (PLD), quetiapine (QTP;), aripiprazole (APZ), dehydroaripiprazole (DAP), olanzapine (OZP), ziprasidone (ZRD), and amisulpride (ASP).MethodsAnalytes and internal standards (ISs) were separated using a Phenomenex phenyl-hexyl column (50.0 × 2.1 mm, 1.7 μm) with water containing 0.1% formic acid and 2 mM ammonium acetate, and methanol containing 0.1% formic acid and 2 mM ammonium acetate as the mobile phase. The antipsychotic drugs and ISs were extracted from 50 μL of plasma using acetonitrile.ResultsThe calibration ranges were 25.0–1500.0 ng/mL for CLP, CPZ, DAP, and QTP, 10.0–600.0 ng/mL for CPZ and ZRD, 2.5–150.0 ng/mL for RPD, 5.0–300.0 ng/mL for PLD and OZP, and 20.0–1200.0 ng/mL for ASP. Validation was carried out according to the guidelines for bioanalytical validation, including assessment of calibration curves, specificity, accuracy, precision, recovery, stability, dilution integrity, and matrix effect. All the results satisfied the requirements.ConclusionThe results provided significant information to support future clinical TDM and rational drug use research. The proposed method also provided a simple, reliable, specific, and suitable technique for TDM and pharmacokinetic studies.

Antipsychotic Potential and Safety Profile of TPGS-Based Mucoadhesive Aripiprazole Nanoemulsion: Development and Optimization for Nose-To-Brain Delivery.

Aripiprazole (APZ) has poor physicochemical properties and bitter taste. The current study aimed to prepare salts of APZ with polycarboxylic acids (citric, malic, and tartaric acids) to improve physicochemical properties and impart sour taste to the drug. The salts were prepared by solubilization-crystallization method, and characterized by electron microscopic, spectroscopic, diffractometry, and thermal methods. The salts were assessed for pH solubility, pH-stability, dissolution, and solid-state stability. Fourier transformed infrared, X-ray powder diffraction, and differential scanning calorimetry data indicated formation of new solid phases. APZ and the salts exhibited pH-dependent solubility. The pH solubility curve shape was inverted "V," inverted "W," and inverted "U" for APZ, APZ-Citrate, and APZ-Malate and APZ-Tartrate, respectively. Compared to APZ, the solubility of salts at pH4, 5, and 6 was 3.6-7.1, 23.9-31.5, and 143.4-373.3 folds of APZ. Increase in solubility in water by citrate, malate, and tartrate salts was 5562.8, 21,284.7, and 22,846.7 folds of APZ. The salt formation also leads to an increase in rate and extent of dissolution. The dissolution extent was 3.5 ± 0.5, 71.3 ± 1.2, 80.1 ± 6.2, and 86.1 ± 1.1% for APZ, APZ-Citrate, APZ-Malate, and APZ-Tartrate, respectively. Liquid and solid-state stabilities of the salts were comparable to APZ. In conclusion, salts of APZ with polycarboxylic acids improved solubility, and dissolution, and impart sour taste, which may improve palatability of the drug.

The present study pursued the systematic development of a stable solid self-emulsifying drug delivery system (SMEDDS) of an atypical antipsychotic drug, aripiprazole (APZ), which exhibits poor aqueous solubility and undergoes extensive p-glycoprotein efflux and hepatic metabolism. Liquid SMEDDS excipients were selected on the basis of solubility studies, and the optimum ratio of surfactant/co-surfactant was determined using pseudo-ternary phase diagrams. The prepared formulations were subjected to in vitro characterization studies to facilitate the selection of optimum liquid SMEDD formulation containing 30% Labrafil® M 1944 CS, 46.7% Cremophor® EL and 23.3% PEG 400 which were further subjected to solidification using maltodextrin as a hydrophilic carrier. The optimized solid SMEDDS was extensively evaluated for stability under accelerated conditions, dissolution at various pH and pharmacokinetic profile. Solid-state attributes of the optimized solid SMEDDS indicated a marked reduction in crystallinity of APZ and uniform adsorption of liquid SMEDDS. Stability study of the solid SMEDDS demonstrated that the developed formulation retained its stability during the accelerated storage conditions. Both the optimized liquid and solid SMEDDS exhibited enhanced dissolution rate which was furthermore independent of the pH of the dissolution medium. Oral bioavailability studies in Sprague-Dawley rats confirmed quicker and greater extent of absorption with solid SMEDDS as evident from the significant reduction in Tmax in case of solid SMEDDS (0.83 ± 0.12h) as compared with commercial tablet (3.33 ± 0.94h). The results of the present investigation indicated the development of a stable solid SMEDDS formulation of APZ with enhanced dissolution and absorption attributes.

Successful treatment with long-acting injectable aripiprazole monohydrate for two patients with dual diagnosis - substance use disorder and psychotic disorder

<p style="text-align: justify;"><strong>Objectives:</strong> Development and evaluation of aripiprazole (AP) loaded lipid based<em> in situ </em>gel system (AP-LIGS) which could maintain the release of drug throughout period circumventing the need of oral therapy. <strong>Materials and Methods: </strong>AP possesses oral bioavailability (~87%) and biological half-life (~75 h) and undergoes extensive first-pass metabolism. Available AP long term injectable preparations have drawback of simultaneous administration of AP tablets orally for first few weeks, leading to patient non-compliance and making the therapy less effective. AP-LIGS was formulated using phospholipid E80, medium chain triglyceride and ethanol. Optimization was done by evaluating the effect of water content on viscosity of prepared AP-LIGS and % cumulative drug release (% CDR) at day 1. <strong>Results: </strong>Optimized AP-LIGS showed rapid gelation with minimum lag time and <em>in vitro</em> drug release profile upto 6 weeks. <em>In vivo </em>depot formation was confirmed by gamma scintigraphy after subcutaneous injection of liquid state of AP-LIGS. Histopathological study revealed its safety and biocompatibility with surrounding tissues since no alteration or any inflammation was observed at the injection site even after 45 days of subcutaneous administration. <em>In vivo </em>neurobehavioral assessment was done for assessing the efficacy of AP-LIGS system using Morris water Maze (MWM) test. MK-801 (Dizocilpine) model was used for inducing schizophrenia in Sprague-Dawley rats. All three parameters escape latency, time spent in target quadrant and total distance travelled was significantly improved (<em>p </em>&lt;0.001) in AP-LIGS group when compared to MK-801 group at all time points. <strong>Conclusion: </strong>Developed novel AP-LIGS system is safe and may be used as a promising approach for sustained drug release and effectively manage schizophrenia. <p style="text-align: justify;"><strong>Key words: </strong> Aripiprazole, Gamma scintigraphy, Injectable, In-situ gel, Phospholipid E80, Schizophrenia.

Interest-Activity Dimension and Response to Aripiprazole

ABSTRACT Introduction Aripiprazole is a third generation antipsychotic approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia. Aripiprazole is available as oral and long-acting injectable (LAI) depot formulations, with a unique mechanism of action comprising partial D2 and serotonin 5-HT1A agonism and antagonism at serotonin 5-HT2A receptors. Areas covered We review short-and-long-term clinical trials, meta-analyses of clinical trials and product information pertaining to the safety and efficacy of aripiprazole in adults with schizophrenia. Formulations of aripiprazole reviewed include oral aripiprazole, Aripiprazole monohydrate LAI (Abilify Maintena©) and Aripiprazole lauroxil LAI (Aristada©). Clinical studies and product information were collected from PubMed, Psychinfo, Embase, and other web sources. Expert opinion Aripiprazole is a generally well-tolerated third-generation antipsychotic with low rates of motor side effects and metabolic adverse effects that occur commonly with several alternative antipsychotics. Akathisia and tremor appear to occur at higher rates with aripiprazole compared to placebo but are still generally uncommon with incidences of 10–11% or less. Uniquely, aripiprazole treatment is associated with reduced serum prolactin levels and QTc interval. A variety of LAI options with dosing intervals as infrequent as every 8 weeks provide a compelling reason to select aripiprazole in patients with limited oral treatment adherence.

To assess adverse events (AEs) and safety of aripiprazole (ARI) and olanzapine (OLA) treatment. Twenty-four healthy volunteers receiving five daily oral doses of 10 mg ARI and 5 mg OLA in a crossover clinical trial were genotyped for 46 polymorphisms in 14 genes by qPCR. Drug plasma concentrations were measured by high-performance liquid chromatography tandem mass spectrometry. Blood pressure (BP) and 12-lead electrocardiogram were measured in supine position. AEs were also recorded. ARI decreased diastolic BP on the first day and decreased QTc on the third and fifth day. OLA had a systolic and diastolic BP, heart rate and QTc lowering effect on the first day. Polymorphisms in ADRA2A, COMT, DRD3 and HTR2A genes were significantly associated to these changes. The most frequent adverse drug reactions (ADRs) to ARI were somnolence, headache, insomnia, dizziness, restlessness, palpitations, akathisia and nausea while were somnolence, dizziness, asthenia, constipation, dry mouth, headache and nausea to OLA. Additionally, HTR2A, HTR2C, DRD2, DRD3, OPRM1, UGT1A1 and CYP1A2 polymorphisms had a role in the development of ADRs. OLA induced more cardiovascular changes; however, more ADRs were registered to ARI. In addition, some polymorphisms may explain the difference in the incidence of these effects among subjects.

Farmakoterapia schizofrenii jest trudnym i złożonym procesem, szczególnie w kontekście objawów negatywnych. Konieczne jest właściwe rozpoznanie grup pacjentów, a w szczególności indywidualnych pacjentów ― w zależności czy objawy negatywne są pierwotne, czy wtórne, przeważające czy znaczące, czy też przeważające i przetrwałe. Piśmiennictwo dotyczące oceny skuteczności różnych leków przeciwpsychotycznych II generacji w leczeniu objawów negatywnych jest niejednorodne, a ocena objawów negatywnych, oparta na różnych metodologiach, dotyczy przede wszystkim różnorodnych grup pacjentów, którzy najprawdopodobniej w zróżnicowany sposób reagują na badane leki, w zależności od tego, czy wykazują znaczące, przeważające lub też przeważające i przetrwałe objawy negatywne. Dodatkowo zdecydowana większość badań dotyczy ogólnej populacji chorych na schizofrenię, wśród których oceniano między innymi nasilenie objawów negatywnych. W związku z tym ocena tych badań i ich porównanie między sobą jest praktycznie niemożliwe. Wybór leku przeciwpsychotycznego II generacji, który wykazywałby zdecydowaną przewagę nad innymi, jest również trudny. W ramach niniejszego opracowania wykonano przegląd literatury dotyczącej badań randomizowanych bezpośrednio porównujących kluczowe leki przeciwpsychotyczne II generacji stosowane w terapii objawów negatywnych. W większości analizowanych badań nie wykazano istotnych statystycznie różnic pomiędzy analizowanymi lekami (porównanie risperidonu, amisulprydu, arypiprazolu, olanzapiny pomiędzy sobą). Tylko w pojedynczych badaniach wykazano przewagę olanzapiny nad risperidonem w ocenie wpływu obu tych leków na objawy negatywne. Należy jednak podkreślić, że wyniki cechowały się ograniczoną wiarygodnością w zakresie możliwości wnioskowania o bezpośrednim wpływie leków na objawy negatywne. Przyczynę takiego stanu rzeczy należy upatrywać między innymi w tym, że w badaniach tych nie korygowano uzyskiwanych efektów o czynniki zakłócające, których wpływ na objawy negatywne został potwierdzony. Natomiast w grupie chorych z przeważającymi i przetrwałymi objawami negatywnymi stwierdza się przewagę kariprazyny nad risperidonem. Uzupełniająca analiza opracowań wtórnych dla analizowanych leków wykazała wyższą skuteczność leków II generacji nad lekami I generacji i placebo w różnych grupach pacjentów z objawami negatywnymi. Należy jednak podkreślić, że badania ze względu na swoją niejednorodność są trudne do porównania. Dodatkowym problemem, który pojawia się w kontekście badań klinicznych, a także codziennej praktyki, jest właściwa diagnoza i odróżnienie pierwotnych objawów negatywnych od wtórnych objawów negatywnych.

Long-acting injectable antipsychotics (LAIs) can potentially reduce hospitalization risk by enhancing medication adherence but are rarely considered for early-phase schizophrenia treatment. To determine whether encouraging use of a LAI compared with usual care delays the time to first hospitalization with patients with early-phase illness. The Prevention of Relapse in Schizophrenia (PRELAPSE) trial was cluster randomized with a follow-up duration of 2 years. The study began in December 2014, was completed in March 2019, and was conducted in 39 mental health centers in 19 US states. Site randomization assigned 19 clinics to encourage treatment with long-acting aripiprazole monohydrate (aripiprazole once monthly [AOM] condition) and 20 to provide treatment as usual (clinician's choice [CC] condition). Participant eligibility criteria included (1) schizophrenia diagnosis confirmed by a structured clinical interview, (2) fewer than 5 years of lifetime antipsychotic use, and (3) age 18 to 35 years. The AOM sites identified 576 potentially eligible participants, of whom 234 (40.6%) enrolled; CC sites identified 685 potentially eligible participants, of whom 255 (37.2%) enrolled. There were no restrictions on treatment at CC sites (including using LAIs) or at AOM sites with the exception that aripiprazole monohydrate had to be prescribed within US Food and Drug Administration-approved guidelines. The primary outcome was time to first psychiatric hospitalization based on participant interviews every 2 months, the service use resource form administered every 4 months, and other sources (eg, health records) as available. Potential events were adjudicated by an independent committee masked to treatment assignment. The 489 participants (368 men [75.3%]) had a mean (SD) age of 25.2 (4.2) years and 225 (46.0%) had 1 year or less lifetime antipsychotic use. Fifty-two AOM (22%) and 91 CC participants (36%) had at least 1 hospitalization. The mean survival time until first hospitalization was 613.7 days (95% CI, 582.3-645.1 days) for AOM participants and 530.6 days (95% CI, 497.3-563.9 days) for CC participants. For time to first hospitalization, the hazard ratio was 0.56 (95% CI, 0.34- 0.92; P = .02), favoring AOM. Survival probabilities were 0.73 (95% CI, 0.65-0.83) for AOM participants and 0.58 (95% CI, 0.50-0.67) for CC participants. The number needed to treat to prevent 1 additional hospitalization was 7 participants treated with AOM compared with CC. Long-acting injectable antipsychotic use by patients with early-phase schizophrenia can significantly delay time to hospitalization, a personally and economically important outcome. Clinicians should more broadly consider LAI treatment for patients with early-phase illness. ClinicalTrials.gov Identifier: NCT02360319.

Aripiprazole (ARP) is one of the newest antipsychotic drugs, exhibiting very low aqueous solubility and high lipophilicity. Considering the necessity of improvement of ARP physicochemical properties and its biopharmaceutical profile, cyclodextrin complexation of the drug substance was performed. As selected cyclodextrin, a functionalized β-cyclodextrin was used, namely heptakis(2,6-di-O-methyl)-β-cyclodextrin (DIMEB), and the supramolecular adduct ARP/DIMEB was prepared by kneading technique and characterized using thermoanalytical tools (TG—thermogravimetry/DTG—derivative thermogravimetry/HF—heat flow), powder X-ray diffractometry patterns (PXRD), universal-attenuated total reflectance Fourier transform infrared (UATR-FTIR) and UV (ultraviolet) spectroscopy and, as well, saturation solubility studies. Job’s method was used for the stoichiometry of APR/DIMEB inclusion complex determination, which was found to be 1:2. Molecular modeling studies were complementary realized as to get a view over the way that ARP is hosted inside the cyclodextrin. The compatibility between the inclusion complex and some common pharmaceutical excipients, namely starch, magnesium stearate, lactose monohydrate, microcrystalline cellulose and methylcellulose, has been evaluated by means of thermal methods of analysis (TG/DTG/HF), UATR-FTIR spectroscopy and PXRD pattern. The preformulation data regarding the compatibility of ARP/DIMEB complex with selected excipients suggested that under ambient conditions, chemical interactions are observed solely between ARP/DIMEB inclusion complex and magnesium stearate, as indicated by the UATR-FTIR spectroscopy. The incompatibility in the system ARP/DIMEB + MgS is also confirmed by the PXRD study, this second investigational technique revealing also the advanced amorphization of components during mixing of complex with starch, microcrystalline cellulose and methylcellulose, but without indicating interactions. Later on, under thermal stress, thermally induced interactions occur between the components in the systems containing magnesium stearate and methylcellulose, while starch, microcrystalline cellulose and lactose can be safely used as excipients in developing solid formulations containing ARP/DIMEB inclusion complex as active pharmaceutical ingredient.

Objective: A simple, rapid, accurate, precise, specific, and sensitive reverse-phase high-performance liquid chromatography (RP-HPLC) method has been developed and validated for simultaneous estimation of olanzapine (OLZ) and aripiprazole (APR) in synthetic mixtures.&#x0D; Methods: The stationary phase used for chromatographic separation was Phenomenex C18 column (250 mm × 4.6 mm i.d, particle size 5 μm) and mobile phase used for separation was methanol: Phosphate buffer (pH 3) taken in ratio of 75:25 %v/v. The flow rate was used 1.0 ml/min at room temperature and drugs detected at 240 nm with injection volume 20 μL.&#x0D; Results: The retention time for OLZ and APR was found to be 4.231 and 6.523 min, respectively. The linearity was performed using a concentration range of 0.5–3.0 for both drugs. The correlation coefficient was found to be 0.999 for OLZ and APR. The % purity of both the drug was found to be 98–102%. The proposed RP-HPLC method has been validated, according to International council on harmonization Q2 (B) guidelines.&#x0D; Conclusion: There was no interference of any diluents and excipients in the determination of drugs from synthetic mixture. Hence, the developed method can be used for routine quality control analysis.

Pharmaceutical cocrystals are a promising strategy to increase the solubility and dissolution rate of poorly soluble drugs. However, their manufacturing process requires a large quantity of solvents. The present study aimed to produce cocrystals by a solvent-free hot melt extrusion (HME) method to improve their solubility and dissolution rate. Aripiprazole (ARP) and adipic acid (ADP) were used as a weakly basic drug and acidic coformer, respectively. The processability of a plain ARP-ADP physical mixture (PM) compared with a PM with 5% Soluplus® (SOL) was investigated. Incorporating 5% SOL into the ARP-ADP blend reduced the processing torque and improved processability. The effects of temperature and screw speed on the formation of cocrystals were studied, and cocrystals were characterized by differential scanning calorimetry (DSC), fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, powder X-ray diffraction (PXRD), scanning electron microscopy, and hot-stage microscopy. FTIR spectra revealed noncovalent interaction between ARP and ADP, which was confirmed by NMR spectra. Similarly, PXRD data exhibited characteristic peaks confirming the formation of new crystalline material. Further, the results indicated that cocrystals demonstrated higher dissolution rates and improved compressibility, as well as enhanced flow characteristics compared with pure ARP, suggesting its suitability in the development of solid dosage forms.

Aripiprazole (ARP) is one of antipsychotics and binds to human serum albumin (HSA) with a high affinity. In this study, we investigated the binding characteristics of ARP to oxidized HSA as observed in chronic disease conditions. Oxidized HSAs were prepared using chloramine-T (CT-HSA) or metal-catalyzed oxidation system (MCO-HSA) in vitro, respectively. An increase in the carbonyl content was confirmed in oxidized HSAs. From the results of circular dichroism (CD) and tryptophan fluorescence spectra, no significant structural change of oxidized HSAs was observed. These results indicate that prepared HSAs are mildly oxidized and well reflects the status of HSA during chronic diseases. However, oxidized HSAs were observed to have a significant decrease in binding to ARP. The results of the induced CD spectrum suggested that ARP bound to oxidized HSAs with a similar orientation. These results suggest that oxidation of HSA during chronic disease state significantly affected the microenvironment of the binding site for ARP and binding capacity of HSA to ARP.

Preparation and evaluation of identifiable quick response (QR)-coded orodispersible films using 3D printer with directly feeding nozzle.