Formulation development and characterization of lumefantrine nanosuspension for enhanced antimalarial activity

Shah, Rajvi; Soni, Tejal; Shah, Unnati; Suhagia, Bhanubhai N.; Patel, Mehul; Patel, Tejas; Gabr, Gamal A.; Gorain, Bapi; Kesharwani, Prashant

doi:10.1080/09205063.2020.1870378

Cited by 19 publications

(6 citation statements)

References 49 publications

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“…Lumefantrine was also investigated as a model compound to understand the dissolution behavior of a weak pharmaceutical base with lower crystallization propensity and less significant pH-dependent solubility than posaconazole. 61 Co-precipitated amorphous dispersions of lumefantrine in Eudragit EPO were prepared at a 25% drug load and found to be fully amorphous by PXRD and have a T g of 38 °C, in between the glass transition temperatures of lumefantrine (T g = 18 °C) and Eudragit EPO (T g = 56 °C), as illustrated in Figure 5. 62 Dispersions stabilized by HPMCAS and VA64 were also prepared by co-precipitation and solvent casting, respectively (see the Supporting Information for characterization).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Dissolution Behavior of Weakly Basic Pharmaceuticals from Amorphous Dispersions Stabilized by a Poly(dimethylaminoethyl Methacrylate) Copolymer

et al. 2022

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Amorphous solid dispersions (ASDs) are a well-documented formulation approach to improve the rate and extent of dissolution for hydrophobic pharmaceuticals. However, weakly basic compounds can complicate standard approaches to ASDs due to pH-dependent solubility, resulting in uncontrolled drug release in gastric conditions and unstabilized supersaturated solutions prone to precipitation at neutral pH. This work examines the release mechanisms of amorphous dispersions containing model weakly basic pharmaceuticals posaconazole and lumefantrine from a basic poly(dimethylaminoethyl methacrylate) copolymer (Eudragit EPO) and compares their dissolution behavior with ASDs stabilized by acidic and neutral polymers to understand potential benefits to release from a basic polymeric stabilizer. It was found that dissolution of Eudragit EPO ASDs resulted in supersaturation under gastric conditions, which could be sustained upon adjustment to neutral pH. However, the dissolution behavior of Eudragit EPO ASDs was sensitive to the initial pH of the gastric media. For lumefantrine, elevated initial gastric pH resulted in precipitation of amorphous nanoparticles; for posaconazole, elevated gastric pH led to crystallization of the pharmaceutical from solution. This sensitivity to gastric pH was found to originate from the impact of Eudragit EPO on gastric pH and the solubility of each pharmaceutical in the first stage of dissolution. In total, these data illustrate benefits and liabilities for the use of Eudragit EPO for ASDs containing weak pharmaceutical bases to guide the design of robust pharmaceutical formulations.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Dissolution Behavior of Weakly Basic Pharmaceuticals from Amorphous Dispersions Stabilized by a Poly(dimethylaminoethyl Methacrylate) Copolymer

et al. 2022

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“…Ganaplacide is combined with lumefantrine, a partner drug used in ACTs for which Novartis now has a new formulation optimized for daily dosing with improved solubility and oral bioavailability. This formulation should help reduce the risk of resistance and maintain efficacy 153 . Novartis announced positive results from an efficacy clinical study with ganaplacide plus the optimized lumefantrine formulation, and a decision to move forward to phase III with the combination has been announced 154 .…”

Section: The Antimalarial Drug Development Pipelinementioning

confidence: 99%

Antimalarial drug discovery: progress and approaches

Siqueira-Neto,

Wicht,

Chibale

et al. 2023

Nat Rev Drug Discov

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Recent antimalarial drug discovery has been a race to produce new medicines that overcome emerging drug resistance, whilst considering safety and improving dosing convenience. Discovery efforts have yielded a variety of new molecules, many with novel modes of action, and the most advanced are in late-stage clinical development. These discoveries have led to a deeper understanding of how antimalarial drugs act, the identification of a new generation of drug targets, and multiple structure-based chemistry initiatives. The limited pool of funding means it is vital to prioritize new drug candidates. They should exhibit high potency, a low propensity for resistance, a pharmacokinetic profile that favours infrequent dosing, low cost, preclinical results that demonstrate safety and tolerability in women and infants, and preferably the ability to block Plasmodium transmission to Anopheles mosquito vectors. In this Review, we describe the approaches that have been successful, progress in preclinical and clinical development, and existing challenges. We illustrate how antimalarial drug discovery can serve as a model for drug discovery in diseases of poverty.

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“…Furthermore, lumefantrine-nanosuspension was active against P. falciparum at exceptionally low concentrations in vitro. The formed nanosuspension has increased solubility, therefore, it was concluded that the nanosuspension can be easily administered by the pediatric and geriatric population, as well as anybody who has difficulty swallowing oral solid dosage forms such as tablets [ 221 ].…”

Section: Nanodrug Delivery Systemsmentioning

confidence: 99%

Current advances in nanodrug delivery systems for malaria prevention and treatment

Kekani

Witika

2023

Discover Nano

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Malaria is a life-threatening, blood-borne disease with over two hundred million cases throughout the world and is more prevalent in Sub-Saharan Africa than anywhere else in the world. Over the years, several treatment agents have been developed for malaria; however, most of these active pharmaceutical ingredients exhibit poor aqueous solubility and low bioavailability and may result in drug-resistant parasites, thus increasing malaria cases and eventually, deaths. Factors such as these in therapeutics have led to a better appreciation of nanomaterials. The ability of nanomaterials to function as drug carriers with a high loading capacity and targeted drug delivery, good biocompatibility, and low toxicity renders them an appealing alternative to conventional therapy. Nanomaterials such as dendrimers and liposomes have been demonstrated to be capable of enhancing the efficacy of antimalarial drugs. This review discusses the recent development of nanomaterials and their benefits in drug delivery for the potential treatment of malaria.

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Formulation development and characterization of lumefantrine nanosuspension for enhanced antimalarial activity

Cited by 19 publications

References 49 publications

Dissolution Behavior of Weakly Basic Pharmaceuticals from Amorphous Dispersions Stabilized by a Poly(dimethylaminoethyl Methacrylate) Copolymer

Dissolution Behavior of Weakly Basic Pharmaceuticals from Amorphous Dispersions Stabilized by a Poly(dimethylaminoethyl Methacrylate) Copolymer

Antimalarial drug discovery: progress and approaches

Current advances in nanodrug delivery systems for malaria prevention and treatment

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