Brain targeted delivery of lurasidone HCl via nasal administration of mucoadhesive nanoemulsion formulation for the potential management of schizophrenia

Patel, Mrunali R.; Patel, Rashmin B.; Thakore, Shivam D.; Solanki, Ajay B.

doi:10.1080/10837450.2020.1772292

Cited by 12 publications

(8 citation statements)

References 36 publications

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“…It acts as an antagonist of dopamine D2 and serotonin 5-HT2A receptors, being a potent drug and having only a weak affinity towards other receptors, hence leading to less extrapyramidal side effects and a reasonably good tolerability profile. Yet, there have still been reports of systemic side effects (elevated levels of serum prolactin, orthostatic hypotension, muscle tremor), and due to having low water solubility (predictably 0.00789 mg/mL) and being highly metabolized, lurasidone also has low oral bioavailability (although improved when taken with food) [ 34 , 53 ]. To improve at least some of these features, Patel et al [ 34 ] decided to formulate lurasidone into O/W nanoemulsions for intranasal administration.…”

Section: Nanometric Emulsions Containing Antipsychotic Drugsmentioning

confidence: 99%

“…Yet, there have still been reports of systemic side effects (elevated levels of serum prolactin, orthostatic hypotension, muscle tremor), and due to having low water solubility (predictably 0.00789 mg/mL) and being highly metabolized, lurasidone also has low oral bioavailability (although improved when taken with food) [ 34 , 53 ]. To improve at least some of these features, Patel et al [ 34 ] decided to formulate lurasidone into O/W nanoemulsions for intranasal administration. Their composition included Capmul ® MCM EP (medium chain mono- and diglycerides), Capmul ® MCM C8 EP (glyceryl monocaprylate), Cremophor ® EL (polyoxyl 35 castor oil) and water (detailed quantities in Table 7 ).…”

Section: Nanometric Emulsions Containing Antipsychotic Drugsmentioning

confidence: 99%

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Antipsychotics-Loaded Nanometric Emulsions for Brain Delivery

2022

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Antipsychotic drugs have numerous disabling side effects, and many are lipophilic, making them hard to formulate at high strength. Incorporating them into nanometric emulsions can increase their solubility, protect them from degradation, and increase their brain delivery, being a promising strategy to overcome the current treatment gap. A thorough review was performed to assess the true potential of these formulations for antipsychotic drugs brain delivery. Intranasal administration was preferred when compared to oral or intravenous administration, since it allowed for direct brain drug transport and reduced systemic drug distribution, having increased efficacy and safety. Moreover, the developed systems increased antipsychotic drug solubility up to 4796 times (when compared to water), which is quite substantial. In the in vivo experiments, nanometric emulsions performed better than drug solutions or suspensions, leading to improved brain drug targeting, mainly due to these formulation’s excipients (surfactants and cosolvents) permeation enhancing capability, added to a small droplet size, which leaves a large surface area available for drug absorption to occur. Thus, even if it is difficult to conclude on which formulation composition leads to a best performance (high number of variables), overall nanometric emulsions have proven to be promising strategies to improve brain bioavailability of antipsychotic drugs.

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Section: Nanometric Emulsions Containing Antipsychotic Drugsmentioning

confidence: 99%

Section: Nanometric Emulsions Containing Antipsychotic Drugsmentioning

confidence: 99%

Antipsychotics-Loaded Nanometric Emulsions for Brain Delivery

2022

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“…Londhe et al [ 38 ] prepared BCD–LRD complexes by kneaded solid dispersion and spray-dried solid dispersion with 1:1 host–guest ratios. Other strategies employed to improve LRD’s solubility include nanosuspensions [ 13 ], co-amorphous complexes [ 39 , 40 , 41 ], hydrotrope formation [ 42 ], and nanoemulsions [ 43 ].…”

Section: Introductionmentioning

confidence: 99%

Improving Lurasidone Hydrochloride’s Solubility and Stability by Higher-Order Complex Formation with Hydroxypropyl-β-cyclodextrin

et al. 2023

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The biopharmaceutical classification system groups low-solubility drugs into two groups: II and IV, with high and low permeability, respectively. Most of the new drugs developed for common pathologies present solubility issues. This is the case of lurasidone hydrochloride—a drug used for the treatment of schizophrenia and bipolar depression. Likewise, the stability problems of some drugs limit the possibility of preparing them in liquid pharmaceutical forms where hydrolysis and oxidation reactions can be favored. Lurasidone hydrochloride presents the isoindole-1,3-dione ring, which is highly susceptible to alkaline hydrolysis, and the benzisothiazole ring, which is susceptible to a lesser extent to oxidation. Herein, we propose to study the increase in the solubility and stability of lurasidone hydrochloride by the formation of higher-order inclusion complexes with hydroxypropyl-β-cyclodextrin. Several stoichiometric relationships were studied at between 0.5 and 3 hydroxypropyl-β-cyclodextrin molecules per drug molecule. The obtained products were characterized, and their solubility and stability were assessed. According to the obtained results, the formation of inclusion complexes dramatically increased the solubility of the drug, and this increased with the increase in the inclusion ratio. This was associated with the loss of crystalline state of the drug, which was in an amorphous state according to infrared spectroscopy, calorimetry, and X-ray analysis. This was also correlated with the stabilization of lurasidone by the cyclodextrin inhibiting its recrystallization. Phase solubility,1H-NMR, and docking computational characterization suggested that the main stoichiometric ratio was 1:1; however, we cannot rule out a 1:2 ratio, where a second cyclodextrin molecule could bind through the isoindole-1,3-dione ring, improving its stability as well. Finally, we can conclude that the formation of higher-order inclusion complexes of lurasidone with hydroxypropyl-β-cyclodextrin is a successful strategy to increase the solubility and stability of the drug.

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“…Lurasidone hydrochloride (LH) was approved by the USFDA in 2007. It is a potent second-generation atypical antipsychotic drug that is used to treat schizophrenia [2,3]. It is utmost efficient in situations where significant concerns include muscle tremors, orthostatic hypotension, and hyperlactatemia.…”

Section: Introductionmentioning

confidence: 99%

“…It is utmost efficient in situations where significant concerns include muscle tremors, orthostatic hypotension, and hyperlactatemia. It possesses good forbearance and minimal extrapyramidal effects due to low affinity towards α, H1, M1, and 5-HT2C receptors [3,4]. It belongs to the class of n-aryl piperazines chemically, which has an improved negative effect on dopamine (D2) and (5-HT2A) serotonergic receptors [5].…”

Section: Introductionmentioning

confidence: 99%

PF-127 Based Niosomal In-situ gel for Intranasal Delivery of Lurasidone Hydrochloride by Surpassing Blood Brain Barrier

Shikalgar,

Deshmukh,

Rathod

et al. 2023

Preprint

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Schizophrenia and Bipolar disorder stand as intense and persistent mental illnesses. This research emphasizes targeted drug delivery through intranasal route via the olfactory lobe by surpass BBB using niosomal thermoreversible gel for precise drug administration. Utilizing a 32 factorial design, Lurasidone hydrochloride niosomes were fabricated through the thin film hydration method. The niosomes underwent assessment to determine their encapsulation efficiency, particle size, zeta potential and polydispersity index whereas thermoreversible niosomal in situ gel based on PF-127 in conjunction with HPMC K4M were characterized for pH, gelation time, temperature responsiveness, in vitro release and rheological characteristics. The results indicated that the optimized batch (F4) illustrated a particle size of 171.4 ± 5.12nm and an encapsulation efficiency 94.67 ± 0.73%. Optimized niosomal gel (Poloxamer 17%) characterized with gelation at 37 ºC, pseudoplastic flow and virtuous structural integrity. Both in vitro and ex vivo drug release exhibited sustained release through in situ gel. These finding concluded that Lurasidone HCL loaded intranasal niosomal in situ gel embraces significant potential to improve inclusive effectiveness of Lurasidone.

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Brain targeted delivery of lurasidone HCl via nasal administration of mucoadhesive nanoemulsion formulation for the potential management of schizophrenia

Cited by 12 publications

References 36 publications

Antipsychotics-Loaded Nanometric Emulsions for Brain Delivery

Antipsychotics-Loaded Nanometric Emulsions for Brain Delivery

Improving Lurasidone Hydrochloride’s Solubility and Stability by Higher-Order Complex Formation with Hydroxypropyl-β-cyclodextrin

PF-127 Based Niosomal In-situ gel for Intranasal Delivery of Lurasidone Hydrochloride by Surpassing Blood Brain Barrier

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