Curcumin micelles entrapped in eudragit S-100 matrix: a synergistic strategy for enhanced oral delivery

Background: Therapeutic activities of curcumin (CUR) via oral administration are hampered by the lack of bioavailability due to its poor water solubility and rapid degradation in GI tract. Materials & methods: This preliminary study developed CUR micelle-eudragit S100 (EUD) dry powder (CM-EDP) spray-dried formulations. Poloxamer 407 was used as a micelle-forming agent and EUD as an entrapping matrix for protection over hydrolysis and enzymes in the GI tract. Results: The morphology of CM-EDP showed agglomeration with cratering on the surface of particles. Differential thermal analysis and x-ray diffractometry data exhibited evidence that CUR was converted into amorphous solid. An increased concentration of micelle-forming and dispersion matrix polymers resulted in a high fraction of drug being converted into the amorphous state. A significant increase in dissolution by 7–10 times was achieved compared with that of raw CUR. Conclusion: The present study disclosed the CM-EDP potency for future development of CUR oral formulation.

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Preclinical Evaluation of UDCA-Containing Oral Formulation in Mice for the Treatment of Wet Age-Related Macular Degeneration

Pharmaceutics ◽

10.3390/pharmaceutics11110561 ◽

2019 ◽

Vol 11 (11) ◽

pp. 561 ◽

Cited By ~ 1

Author(s):

Maharjan ◽

Kim ◽

Jin ◽

Ko ◽

Song ◽

...

Keyword(s):

Macular Degeneration ◽

Oral Delivery ◽

Water Solubility ◽

Vision Loss ◽

Oral Absorption ◽

Aqueous Solubility ◽

Oral Formulation ◽

Preclinical Study ◽

Age Related Macular Degeneration ◽

Age Related

As a posterior ocular disease, wet age-related macular degeneration (WAMD) has been known to be related to vision loss, accompanying ocular complications. The intravitreous injection of VEGF antibodies has been reported to be an effective treatment to relieve symptoms of WAMD. However, the limitations of this treatment are high costs and invasiveness. For this reason, oral delivery route can be considered as a cost-effective way and the safest method to deliver drug molecules to the eyes. Accordingly, ursodeoxycholic acid (UDCA) was included in the oral formulation as the potential substance for the cure of WAMD in the animal model. Various pharmacological activities, such as antioxidant or anti-inflammatory effects, have been reported for UDCA and recent reports support the effects of UDCA in ocular treatment. However, due to poor water solubility and low pKa (around 5.0), it has been challenging to formulate aqueous solution of UDCA in the neutral pH range. In the present study, we confirmed the aqueous solubility of the oral UDCA formulation and performed a preclinical study, including pharmacokinetic profiling and WAMD model efficacy study in mice after oral administration of the drug solution. The results demonstrated that the formulation improved bioavailability of UDCA and efficiently delivered UDCA to the eye tissues after oral absorption. UDCA formulation was found to have inhibitory effects of choroidal neovascularization with a functional recovery in mice retinas. Taken together, our results suggest that the oral UDCA formulation could be used as a potent supplement for the cure of WAMD and related retinal diseases.

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Lipid Systems for the Delivery of Amphotericin B in Antifungal Therapy

Pharmaceutics ◽

10.3390/pharmaceutics12010029 ◽

2020 ◽

Vol 12 (1) ◽

pp. 29 ◽

Cited By ~ 14

Author(s):

Faustino ◽

Pinheiro

Keyword(s):

Side Effects ◽

Amphotericin B ◽

Targeted Delivery ◽

Oral Delivery ◽

Water Solubility ◽

Therapeutic Potential ◽

Fungal Infections ◽

Cost Effective ◽

Oral Formulation ◽

Life Threatening

Amphotericin B (AmB), a broad-spectrum polyene antibiotic in the clinic for more than fifty years, remains the gold standard in the treatment of life-threatening invasive fungal infections and visceral leishmaniasis. Due to its poor water solubility and membrane permeability, AmB is conventionally formulated with deoxycholate as a micellar suspension for intravenous administration, but severe infusion-related side effects and nephrotoxicity hamper its therapeutic potential. Lipid-based formulations, such as liposomal AmB, have been developed which significantly reduce the toxic side effects of the drug. However, their high cost and the need for parenteral administration limit their widespread use. Therefore, delivery systems that can retain or even enhance antimicrobial efficacy while simultaneously reducing AmB adverse events are an active area of research. Among those, lipid systems have been extensively investigated due to the high affinity of AmB for binding lipids. The development of a safe and cost-effective oral formulation able to improve drug accessibility would be a major breakthrough, and several lipid systems for the oral delivery of AmB are currently under development. This review summarizes recent advances in lipid-based systems for targeted delivery of AmB focusing on non-parenteral nanoparticulate formulations mainly investigated over the last five years and highlighting those that are currently in clinical trials.

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Nanostructured lipid carriers- A versatile carrier for oral delivery of lipophilic drugs

Recent Patents on Nanotechnology ◽

10.2174/1872210514666200909154959 ◽

2020 ◽

Vol 14 ◽

Author(s):

Priyanshi Patel ◽

Mitali Patel

Keyword(s):

Oral Bioavailability ◽

Oral Delivery ◽

Water Solubility ◽

Oral Formulation ◽

Lipid Nanoparticles ◽

Nanostructured Lipid Carriers ◽

Lipophilic Drugs ◽

Promising Tool ◽

Pharmaceutical Industries

Background: Around 40% of newly discovered chemical entities in pharmaceutical industries have poor water solubility and hence they suffer from low oral bioavailability owing to undesirable physicochemical and pharmacokinetic properties. So, it is the challenge for the formulation scientists to develop the oral formulation that can mitigate the pitfalls associated with such lipophilic drugs. Methods: Lipid nanoparticles hold a promising tool to augment the pitfalls of lipophilic drugs as lipid component can effectively increases the absorption of drugs which leads to improvement in oral bioavailability. They are also considered as safe because they are made up of physiological lipids which are biocompatible and biodegradable in nature. Amongst the lipid nanoparticles, Nanostructured lipid carriers (NLCs) are the second-generation lipid nanoparticle and were developed to conquer the limitations of solid lipid nanoparticles. They increase the solubility, permeability, reduce metabolism, P-glycoprotein efflux and thereby increase the bioavailability of poorly soluble drugs. Conclusion: This review highlights the various aspects of NLCs such as formulation components, types, in vivo fate, Pharmacokinetic, toxicity, recent advances and patent review of NLCs in drug delivery.

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Overcoming clofazimine intrinsic toxicity: statistical modelling and characterization of solid lipid nanoparticles

Journal of The Royal Society Interface ◽

10.1098/rsif.2017.0932 ◽

2018 ◽

Vol 15 (139) ◽

pp. 20170932 ◽

Cited By ~ 6

Author(s):

Luíse L. Chaves ◽

Sofia Lima ◽

Alexandre C. C. Vieira ◽

Domingos Ferreira ◽

Bruno Sarmento ◽

...

Keyword(s):

Solid Lipid Nanoparticles ◽

Oral Delivery ◽

Water Solubility ◽

Oral Drug Delivery ◽

Drug Loading ◽

Amorphous State ◽

Lipid Nanoparticles ◽

Oral Drug ◽

Solid Lipid ◽

Cytotoxicity Studies

The aim of this work was to develop solid lipid nanoparticles (SLNs) loaded with clofazimine (CLZ) (SLNs-CLZ) to overcome its intrinsic toxicity and low water solubility, for oral drug delivery. A Box–Behnken design was constructed to unravel the relations between the independent variables in the selected responses. The optimized SLNs-CLZ exhibited the following properties: particle size ca 230 nm, zeta potential of −34.28 mV, association efficiency of 72% and drug loading of 2.4%, which are suitable for oral delivery. Further characterization included Fourier transformed infrared spectroscopy that confirmed the presence of the drug and the absence of chemical interactions. By differential scanning calorimetry was verified the amorphous state of CLZ. The storage stability studies ensured the stability of the systems over a period of 12 weeks at 4°C. In vitro cytotoxicity studies evidenced no effect of both drug-loaded and unloaded SLNs on MKN-28 gastric cells and on intestinal cells, namely Caco-2 and HT29-MTX cells up to 25 µg ml −1 in CLZ. Free CLZ solutions exhibited IC 50 values of 16 and 20 µg ml −1 for Caco-2 and HT29-MTX cells, respectively. It can be concluded that the optimized system, designed considering important variables for the formulation of poorly soluble drugs, represents a promising platform for oral CLZ delivery.

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Polymeric Micelles, a Promising Drug Delivery System to Enhance Bioavailability of Poorly Water-Soluble Drugs

Journal of Drug Delivery ◽

10.1155/2013/340315 ◽

2013 ◽

Vol 2013 ◽

pp. 1-15 ◽

Cited By ~ 190

Author(s):

Wei Xu ◽

Peixue Ling ◽

Tianmin Zhang

Keyword(s):

Drug Delivery ◽

Residence Time ◽

Oral Delivery ◽

Polymeric Micelles ◽

Water Soluble ◽

Gi Tract ◽

Poorly Water Soluble Drugs ◽

Water Soluble Drugs ◽

Poorly Water Soluble ◽

Accepted Form

Oral administration is the most commonly used and readily accepted form of drug delivery; however, it is find that many drugs are difficult to attain enough bioavailability when administered via this route. Polymeric micelles (PMs) can overcome some limitations of the oral delivery acting as carriers able to enhance drug absorption, by providing (1) protection of the loaded drug from the harsh environment of the GI tract, (2) release of the drug in a controlled manner at target sites, (3) prolongation of the residence time in the gut by mucoadhesion, and (4) inhibition of efflux pumps to improve the drug accumulation. To explain the mechanisms for enhancement of oral bioavailability, we discussed the special stability of PMs, the controlled release properties of pH-sensitive PMs, the prolongation of residence time with mucoadhesive PMs, and the P-gp inhibitors commonly used in PMs, respectively. The primary purpose of this paper is to illustrate the potential of PMs for delivery of poorly water-soluble drugs with bioavailability being well maintained.

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Relative Contributions of Solubility and Mobility to the Stability of Amorphous Solid Dispersions of Poorly Soluble Drugs: A Molecular Dynamics Simulation Study

Pharmaceutics ◽

10.3390/pharmaceutics10030101 ◽

2018 ◽

Vol 10 (3) ◽

pp. 101 ◽

Cited By ~ 7

Author(s):

Michael Brunsteiner ◽

Johannes Khinast ◽

Amrit Paudel

Keyword(s):

Molecular Dynamics ◽

Oral Delivery ◽

Solid Dispersions ◽

Amorphous Solid ◽

Dynamics Simulation ◽

Limiting Factor ◽

Poorly Soluble Drugs ◽

Formulation Development ◽

Amorphous Solid Dispersions ◽

Poorly Soluble

Amorphous solid dispersions are considered a promising formulation strategy for the oral delivery of poorly soluble drugs. The limiting factor for the applicability of this approach is the physical (in)stability of the amorphous phase in solid samples. Minimizing the risk of reduced shelf life for a new drug by establishing a suitable excipient/polymer-type from first principles would be desirable to accelerate formulation development. Here, we perform Molecular Dynamics simulations to determine properties of blends of eight different polymer–small molecule drug combinations for which stability data are available from a consistent set of literature data. We calculate thermodynamic factors (mixing energies) as well as mobilities (diffusion rates and roto-vibrational fluctuations). We find that either of the two factors, mobility and energetics, can determine the relative stability of the amorphous form for a given drug. Which factor is rate limiting depends on physico-chemical properties of the drug and the excipients/polymers. The methods outlined here can be readily employed for an in silico pre-screening of different excipients for a given drug to establish a qualitative ranking of the expected relative stabilities, thereby accelerating and streamlining formulation development.

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DEVELOPMENT OF MICROEMULSION FORMULATION FOR ORAL DELIVERY OF ROSUVASTATIN CALCIUM

International Journal of Pharmaceutical Sciences and Drug Research ◽

10.25004/ijpsdr.2020.120106 ◽

2020 ◽

pp. 35-39

Author(s):

Himanshu Paliwal ◽

Ram Singh Solanki ◽

Chetan Singh Chauhan

Keyword(s):

Zeta Potential ◽

Droplet Size ◽

Oral Delivery ◽

Water Solubility ◽

Tween 80 ◽

In Vitro Dissolution ◽

Microemulsion Formulation ◽

Polyethylene Glycol 400 ◽

Rosuvastatin Calcium

The purpose of conducting this study was to prepare an oral microemulsion formulation of Rosuvastatin calcium (RC) to improve its water solubility. Oil in water microemulsion was formulated using Oleic acid, Tween 80 and Polyethylene Glycol-400(PEG-400) as oil, surfactant and co-surfactant, respectively. The ideal proportion of surfactant: co-surfactant (Smix) was chosen by constructing pseudoternary diagrams. The microemulsion formulations which proved to be stable after thermodynamic stability testing were further evaluated for physical characteristics. Selected formulations were evaluated for droplet size, zeta potential, polydispersity index, viscosity and % drug content. The results were suggestive that optimized microemulsion formulation (F2) was thermodynamically stable and clear having a droplet size of 74.29 nm and zeta potential of -18.44. In vitro dissolution study for optimized microemulsion was performed using a dialysis bag method and cumulative % drug release was determined. The result from the release study was indicative of improved solubility of Rosuvastatin calcium which may serve to boost up the oral bioavailability of drug.

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Contribution to the Improvement of an Oral Formulation of Niclosamide, an Antihelmintic Drug Candidate for Repurposing in SARS-CoV-2 and Other Viruses

10.26434/chemrxiv.12056187.v1 ◽

2020 ◽

Author(s):

Eduardo José Barbosa ◽

Mariana Ribeiro Gubitoso ◽

Nádia Araci Bou-Chacra ◽

Stephen R. Byrn ◽

Flavio M. S. Carvalho ◽

...

Keyword(s):

Solid Dispersions ◽

Amorphous Solid ◽

Aqueous Solubility ◽

Oral Formulation ◽

Oral Dosage ◽

Drug Candidate ◽

Formulation Development ◽

Polymer Dispersions ◽

Kinetic Solubility ◽

Oral Dosage Forms

<p>Niclosamide (NCL) is an effective anthelmintic agent that has been shown to possess broad-spectrum antiviral activity, including against<b> </b>SARS-CoV-2. Due to its poor solubility in aqueous medium, however, the commercially available NCL formulations can act only locally in gastrointestinal worms and are not suitable to achieve plasmatic levels to treat systemic diseases. Consequently, the repurposing of this drug represents a challenge for formulation development with serious risks to the biological availability and can compromise preclinical and clinical outcomes. Herein, we report possible formulation, through the research and development, of stable amorphous solid dispersions to improve its solubility. The results of exploratory screening of NCL-polymer dispersions (performed through X-ray powder diffraction and kinetic solubility studies) indicate that soluplus-niclosamide dispersions can increase its aqueous solubility and, consequently, have the potential to enhance NCL bioavailability. <a>This outcome can be used for the development of oral dosage forms for clinical trials in SARS-CoV-2 and other viruses. </a></p>

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Solubility and Dissolution Enhancement of Atorvastatin Calcium using Solid Dispersion Adsorbate Technique

Iraqi Journal of Pharmaceutical Sciences ( P-ISSN 1683 - 3597 E-ISSN 2521 - 3512) ◽

10.31351/vol28iss2pp105-114 ◽

2019 ◽

Vol 28 (2) ◽

pp. 105-114

Author(s):

Samer K. Ali ◽

Eman B. H. Al-Khedairy

Keyword(s):

Polyethylene Glycol ◽

Solid Dispersion ◽

Water Solubility ◽

Drug Carrier ◽

Solid Dispersions ◽

Poloxamer 407 ◽

Dissolution Enhancement ◽

Drug Solubility ◽

Scanning Calorimetry ◽

Poorly Soluble

Atorvastatin (ATR) is poorly soluble anti-hyperlipidemic drug; it belongs to the class II group according to the biopharmaceutical classification system (BCS) with low bioavailability due to its low solubility. Solid dispersions adsorbate is an effective technique for enhancing the solubility and dissolution of poorly soluble drugs. The present study aims to enhance the solubility and dissolution rate of ATR using solid dispersion adsorption technique in comparison with ordinary solid dispersion. polyethylene glycol 4000 (PEG 4000), polyethylene glycol 6000 (PEG 6000), Poloxamer188 and Poloxamer 407were used as hydrophilic carriers and Aerosil 200, Aerosil 300 and magnesium aluminium silicate (MAS) as adsorbents. All solid dispersion adsorbate (SDA) formulas were prepared in ratios of 1:1:1 (drug: carrier: adsorbent) and evaluated for their water solubility, percentage yield, drug content, , dissolution, crystal structure using X-ray powder diffraction (XRD) and Differential Scanning Calorimetry (DSC) studies and Fourier Transform Infrared Spectroscopy (FTIR) for determination the drug-carrier- adsorbate interaction. The prepared (SDA) showed significant improvement of drug solubility in all prepared formula. Best result was obtained with formula SDA12(ATR :Poloxamer407 : MAS 1:1:1) that showed 8.07 and 5.38 fold increase in solubility compared to solubility of pure ATR and solid dispersion(SD4) (Atorvastatin: Poloxamer 407 1:1) respectively due to increased wettability and reduced crystallinity of the drug which leads to improve drug solubility and dissolution .

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Engineering Advances in Spray Drying for Pharmaceuticals

Annual Review of Chemical and Biomolecular Engineering ◽

10.1146/annurev-chembioeng-091720-034106 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

John M. Baumann ◽

Molly S. Adam ◽

Joel D. Wood

Keyword(s):

Spray Drying ◽

Oral Delivery ◽

Process Development ◽

Solid Dispersions ◽

Amorphous Solid ◽

Annual Review ◽

Publication Date ◽

Dry Powders ◽

Wide Range ◽

Pharmaceutical Industries

Spray drying is a versatile technology that has been applied widely in the chemical, food, and, most recently, pharmaceutical industries. This review focuses on engineering advances and the most significant applications of spray drying for pharmaceuticals. An in-depth view of the process and its use is provided for amorphous solid dispersions, a major, growing drug-delivery approach. Enhanced understanding of the relationship of spray-drying process parameters to final product quality attributes has made robust product development possible to address a wide range of pharmaceutical problem statements. Formulation and process optimization have leveraged the knowledge gained as the technology has matured, enabling improved process development from early feasibility screening through commercial applications. Spray drying's use for approved small-molecule oral products is highlighted, as are emerging applications specific to delivery of biologics and non-oral delivery of dry powders. Based on the changing landscape of the industry, significant future opportunities exist for pharmaceutical spray drying. Expected final online publication date for the Annual Review of Chemical and Biomolecular Engineering, Volume 12 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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