scholarly journals Facile methodology of nanoemulsion preparation using oily polymer for the delivery of poorly soluble drugs

2019 ◽  
Vol 10 (5) ◽  
pp. 1228-1240 ◽  
Author(s):  
Johanna Wik ◽  
Kuldeep K. Bansal ◽  
Tatu Assmuth ◽  
Ari Rosling ◽  
Jessica M. Rosenholm
Keyword(s):  
High Speed ◽  
Aqueous Solubility ◽  
Active Pharmaceutical Ingredient ◽  
Poorly Soluble Drugs ◽  
Cytotoxicity Studies ◽  
Nanoprecipitation Method ◽  
Different Temperatures ◽  
Poorly Soluble ◽  
Conventional Oils ◽  
Thermodynamic Instability

AbstractAqueous solubility of an active pharmaceutical ingredient (API) is a determining factor that has a direct impact on formulation strategies and overall bioavailability. Fabrication of nanoemulsions of poorly soluble drugs is one of the widely utilized approaches to overcome this problem. However, thermodynamic instability and tedious manufacturing processes of nanoemulsions limit their clinical translation. Therefore, this study was focused on circumventing the abovementioned hurdles by utilizing the polymer as an oil phase, instead of conventional oils. The nanoemulsion was prepared via a facile low-energy nanoprecipitation method using renewable poly(δ-decalactone) (PDL), as an oil phase and Pluronic F-68 as surfactant. The prepared nanoemulsions were characterized in terms of size, drug encapsulation efficiency, stability, and toxicity. Five different hydrophobic drugs were utilized to evaluate the drug delivery capability of the PDL nanoemulsion. The prepared nanoemulsions with sizes less than 200 nm were capable to enhance the aqueous solubility of the drugs by 3 to 10 times compared with the well-established Pluronic F-68 micelles. No phase separation or significant changes in size and drug content was observed with PDL nanoemulsions after high-speed centrifugation and 3 months of storage at two different temperatures (20 °C and 50 °C). PDL nanoemulsions were found to be non-heamolytic up to concentrations of 1 mg/mL, and the cell cytotoxicity studies on MDA-MB-231 and MEF cells suggest a concentration and time-dependent toxicity, where the PDL polymer itself induced no cytotoxicity. The results from this study clearly indicate that the PDL polymer has a tremendous potential to be utilized as an oil phase to prepare stable nanoemulsions via a facile methodology, ultimately favouring clinical translations.

Self-microemulsion Technology for Water-insoluble Drug Delivery

2019 ◽  
Vol 15 (6) ◽  
pp. 576-588 ◽  
Author(s):  
Beibei Yan ◽  
Yu Gu ◽  
Juan Zhao ◽  
Yangyang Liu ◽  
Lulu Wang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Aqueous Solubility ◽  
Delivery Systems ◽  
Poorly Soluble Drugs ◽  
New Chemical Entities ◽  
Poorly Soluble ◽  
Water Insoluble Drug ◽  
Semi Solid ◽  
Solidification Technology

: According to the drug discovery, approximately 40% of the new chemical entities show poor bioavailability due to their low aqueous solubility. In order to increase the solubility of the drugs, self-micro emulsifying drug delivery systems (SMEDDS) are considered as an ideal technology for enhancing the permeability of poorly soluble drugs in GI membranes. The SMEDDS are also generally used to enhance the oral bioavailability of the hydrophobic drugs. At present, most of the self-microemulsion drugs are liquid dosage forms, which could cause some disadvantages, such as the low bioavailability of the traditional liquid SMEDDS. Therefore, solid self-micro emulsifying drug delivery systems (S-SMEDDS) have emerged widely in recent years, which were prepared by solidifying a semi-solid or liquid self-emulsifying (SE) ingredient into a powder in order to improve stability, treatment and patient compliance. The article gives a comprehensive introduction of the study of SMEDDS which could effectively tackle the problem of the water-insoluble drug, especially the development of solidification technology of SMEDDS. Finally, the present challenges and the prospects in this field were also discussed.

Enhancement the Dissolution Rate and Solubility of Poorly Soluble Drugs: Review

2013 ◽  
Vol 701 ◽  
pp. 234-238 ◽  
Author(s):  
Mubarak Abdullah Saleh ◽  
Salam A. Mohammed ◽  
Ezzat C Abdullah ◽  
Laith A. Hashim
Keyword(s):  
Drug Delivery ◽  
Chemical Composition ◽  
Active Pharmaceutical Ingredient ◽  
Nucleation Mechanism ◽  
Rapid Freezing ◽  
Poorly Soluble Drugs ◽  
Pharmaceutical Development ◽  
Drug Products ◽  
Poorly Soluble ◽  
As Solubility

The use of reduction and nucleation technologies in nanosize active pharmaceutical ingredient (API) is as an enabling to bring improved drug products to the marketplace demand as well as for improved drug delivery. nanoPharmaceutical field represents a hopeful set of pharmaceutical materials offering the prospect of better alternatives to optimize drug physical properties and biopharmaceutical issues such as solubility, stability and bioavailability in pharmaceutical development without changing the chemical composition of the API, thereby, giving new patentable solid forms. With physically improved solid API may impact the the pharmaceutical intellectual property landscape. Nanoparticle formation is achievable in many ways, although primarily through particle reduction or through manipulation of the nucleation mechanism. Keywords: active pharmaceutical ingredient; drug delivery; ultra rapid freezing.

scholarly journals Cheminformatics-driven discovery of polymeric micelle formulations for poorly soluble drugs

2019 ◽  
Vol 5 (6) ◽  
pp. eaav9784 ◽  
Author(s):  
Vinicius M. Alves ◽  
Duhyeong Hwang ◽  
Eugene Muratov ◽  
Marina Sokolsky-Papkov ◽  
Ekaterina Varlamova ◽  
...  
Keyword(s):  
Prediction Accuracy ◽  
Drug Loading ◽  
Aqueous Solubility ◽  
Polymeric Micelle ◽  
Loading Capacity ◽  
Poorly Soluble Drugs ◽  
Polymer Complexes ◽  
Drug Candidates ◽  
Therapeutic Development ◽  
Poorly Soluble

Many drug candidates fail therapeutic development because of poor aqueous solubility. We have conceived a computer-aided strategy to enable polymeric micelle-based delivery of poorly soluble drugs. We built models predicting both drug loading efficiency (LE) and loading capacity (LC) using novel descriptors of drug-polymer complexes. These models were employed for virtual screening of drug libraries, and eight drugs predicted to have either high LE and high LC or low LE and low LC were selected. Three putative positives, as well as three putative negative hits, were confirmed experimentally (implying 75% prediction accuracy). Fortuitously, simvastatin, a putative negative hit, was found to have the desired micelle solubility. Podophyllotoxin and simvastatin (LE of 95% and 87% and LC of 43% and 41%, respectively) were among the top five polymeric micelle-soluble compounds ever studied experimentally. The success of the strategy described herein suggests its broad utility for designing drug delivery systems.

scholarly journals Ionic Liquid-Polymer Nanoparticle Hybrid Systems as New Tools to Deliver Poorly Soluble Drugs

Nanomaterials ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 1148 ◽  
Author(s):  
Ana Júlio ◽  
Rita Caparica ◽  
Sofia A. Costa Lima ◽  
Ana Sofia Fernandes ◽  
Catarina Rosado ◽  
...  
Keyword(s):  
Hybrid Systems ◽  
Delivery System ◽  
Freeze Drying ◽  
Poorly Soluble Drugs ◽  
Drug Solubility ◽  
New Paradigm ◽  
Polymer Nanoparticle ◽  
Liquid Polymer ◽  
Cytotoxicity Studies ◽  
Poorly Soluble

The use of functional excipients such as ionic liquids (ILs) and the encapsulation of drugs into nanocarriers are useful strategies to overcome poor drug solubility. The aim of this work was to evaluate the potential of IL-polymer nanoparticle hybrid systems as tools to deliver poorly soluble drugs. These systems were obtained using a methodology previously developed by our group and improved herein to produce IL-polymer nanoparticle hybrid systems. Two different choline-based ILs and poly (lactic-co-glycolic acid) (PLGA) 50:50 or PLGA 75:25 were used to load rutin into the delivery system. The resulting rutin-loaded IL-polymer nanoparticle hybrid systems presented a diameter of 250–300 nm, with a low polydispersity index and a zeta potential of about −40 mV. The drug association efficiency ranged from 51% to 76%, which represents a good achievement considering the poor solubility of rutin. No significant particle aggregation was obtained upon freeze-drying. The presence of the IL in the nanosystem does not affect its sustained release properties, achieving about 85% of rutin released after 72 h. The cytotoxicity studies showed that the delivery system was not toxic to HaCat cells. Our findings may open a new paradigm on the therapy improvement of diseases treated with poorly soluble drugs.

scholarly journals Hydrotropic Solubilization: An Emerging Approach

2021 ◽  
Vol 11 (1-s) ◽  
pp. 200-206
Author(s):  
Ashwin Bhanudas Kuchekar ◽  
Ashwini Gawade ◽  
Sanjay Boldhane
Keyword(s):  
Patient Safety ◽  
Aqueous Solubility ◽  
Oral Route ◽  
Poorly Soluble Drugs ◽  
Gastrointestinal Mucosa ◽  
Optimal Drug ◽  
Insoluble Drugs ◽  
Poorly Soluble ◽  
Poor Absorption ◽  
Low Solubility

Drug development plays an important role in patient safety and effectiveness. The therapeutic suitability of a new drug depends on the solubility. The solubility of the sparingly soluble drug remains a problem in identifying new active compounds. Solubility plays an important role in achieving optimal drug concentration. Low solubility is not only a concern for the production of formulations, but also an obstacle from the outset when identifying active chemicals for therapeutic purposes. Due to its simplicity in terms of ease of administration and economy, the oral route is the preferred route of drug administration over other routes. Effective aqueous solubility is the first prerequisite for oral medication, since low solubility has poor absorption and bioavailability and unpredictable toxicity of the gastrointestinal mucosa. To avoid these crises, different methodologies are used to improve the solubility and bioavailability of poorly soluble drugs, and hydrotropic solubilization is one of them. Hydrotropic agents have the potential to improve the solubility of water-insoluble drugs. In this review, we try to address hydrotropic solubilization methodologies. Keywords: Hydrotropy, Micelles, Solubility, Formulation.

Enhanced Oral Bioavailability of Ibrutinib Encapsulated Poly (Lactic-co- Glycolic Acid) Nanoparticles: Pharmacokinetic Evaluation in Rats

2019 ◽  
Vol 15 (6) ◽  
pp. 661-668 ◽  
Author(s):  
Abdullah S. Alshetaili ◽  
Mohammad J. Ansari ◽  
Md. K. Anwer ◽  
Majid A. Ganaie ◽  
Muzaffar Iqbal ◽  
...  
Keyword(s):  
Oral Bioavailability ◽  
Compartmental Analysis ◽  
Aqueous Solubility ◽  
Plga Nanoparticles ◽  
Albino Rats ◽  
Maximum Plasma ◽  
Nanoprecipitation Method ◽  
Poorly Soluble ◽  
Development Phases ◽  
Wistar Albino Rats

Background: The poor oral bioavailability of newly discovered chemical entities and marketed formulations are usually related to poor aqueous solubility or poor permeability, leading to drug failure in the development phases or therapeutic failure in a clinical setting. However, advancement in drug formulations and delivery technologies have enabled scientists to improve the bioavailability of formulations by enhancing solubility or permeability. Objective: This study reports the enhancement of the oral bioavailability of ibrutinib (IBR), a poorly soluble anticancer drug in Wistar albino rats. Methods: IBR loaded nanoparticles were formulated through the nanoprecipitation method by utilizing poly lactide-co-glycolide (PLGA) as a safe, biodegradable and biocompatible polymer, and poloxamer or pluronic 127 as a stabilizer. Animals were administered with a dose of 10 mg/kg of IBR suspension or an equivalent amount of IBR loaded nanoparticles. Plasma samples were extracted and analyzed by state of the art UPLC-MS/MS technique. Pharmacokinetic (PK) parameters and bioavailability were calculated by non-compartmental analysis. Results: There was an approximately 4.2-fold enhancement in the oral bioavailability of IBR-loaded nanoparticles, as compared to the pure IBR suspension. The maximum plasma concentration (Cmax; 574.31 ± 56.20 Vs 146.34 ± 5.37 ng/mL) and exposure (AUC; 2291.65 ± 263.83 vs 544.75 ± 48.33 ng* h/mL) of IBR loaded nanoparticles were significantly higher than those exhibited through pure IBR suspension. Conclusion: The outcomes of the present study suggested the potential of PLGA nanoparticles in the enhancement of bioavailability and the therapeutic efficacy of IBR.

Solubility Enhancement of Poorly Soluble Drug Simvastatin by Solid Dispersion Technique

2016 ◽  
Vol 2 (2) ◽  
pp. 91-95
Author(s):  
Neelima Rani T ◽  
Pavani A ◽  
Sobhita Rani P ◽  
Srilakshmi N
Keyword(s):  
Dissolution Rate ◽  
Drug Carrier ◽  
Solid Dispersions ◽  
Aqueous Solubility ◽  
Onset Of Action ◽  
Kneading Method ◽  
Wetting Property ◽  
Poorly Soluble ◽  
Dispersion Technique ◽  
Low Solubility

This study aims to formulate solid dispersions (SDs) of Simvastatin (SIM) to improve the aqueous solubility, dissolution rate and to facilitate faster onset of action. Simvastatin is a BCS class II drug having low solubility & therefore low oral bioavailability. In the present study, SDs of simvastatin different drug-carrier ratios were prepared by kneading method. The results showed that simvastatin solubility & dissolution rate enhanced with polymer SSG in the ratio 1:7 due to increase in wetting property or possibly may be due to change in crystallinity of the drug.

Technological Advancements in Oral Films

2019 ◽  
Vol 9 (01) ◽  
pp. 15-20
Author(s):  
B Pandey ◽  
A B Khan
Keyword(s):  
3D Printing ◽  
Historical Background ◽  
Poorly Soluble Drugs ◽  
Modern Approach ◽  
Poorly Soluble ◽  
Critical Process Parameters ◽  
Biopharmaceutical Properties ◽  
Oral Films ◽  
Hot Melt ◽  
Modern Technologies

The aim of the review was to explore the necessity, advantages and different techniques of oral films for enhancing solubility of poorly soluble drugs with an emphasis on the newer, state-of the art technologies, such as 3D printing and hot-melt extrusion (HME). The historical background of oral films is presented along with the regularly used techniques. The modern approach of quality-by-design (QbD) is unravelled, identifying appropriate critical process parameters (CPP) and applied to oral films. A section is devoted modern technologies such as 3D printing and HME of oral films. Oral films are innovative formulations by which poorly soluble drugs have been founds to give positive results in enhancing their solubility and dissolution characteristics. With modern sophisticated techniques, precise mass production of oral films has been given a thrust. Oral films have better patient compliance, improved biopharmaceutical properties, improved efficacy, and better safety. By applying QbD and implementation of modern technologies the newer generation of oral films are yielding promising results

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