Effects of Different Formulation Methods on Drug Crystallinity, Drug-Carrier Interaction, and Ex Vivo Permeation of a Ternary Solid Dispersion Containing Nisoldipine

Ternary Solid Dispersion Strategy for Solubility Enhancement of Poorly Soluble Drugs by Co-Milling Technique

10.5772/intechopen.95518 ◽

2021 ◽

Author(s):

Marouene Bejaoui ◽

Hanen Oueslati ◽

Haykel Galai

Keyword(s):

Solid Dispersion ◽

Drug Carrier ◽

Water Soluble ◽

Pharmaceutical Ingredients ◽

Drug Molecules ◽

Water Soluble Drugs ◽

Milling Method ◽

Ternary Solid Dispersion

Amorphous ternary solid dispersion has become one of the strategies commonly used for improving the solubility and bioavailability of poorly water soluble drugs. Such multicomponent solid dispersion can be obtained by different techniques, this chapter provides an overview of ternary solid dispersion by co-milling method from the perspectives of physico-chemical characteristics in vitro and in vivo performance. A considerable improvement of solubility was obtained for many active pharmaceutical ingredients (e.g., Ibuprofen, Probucol, Gliclazid, Fenofibrate, Ibrutinib and Naproxen) and this was correlated to the synergy of multiple factors (hydrophilicity enhancement, particle size reduction, drug-carrier interactions, anti-plasticizing effect and complexation efficiency). This enhanced pharmacokinetic properties and bioavailability of these drug molecules (1.49 to 15-folds increase in plasma drug concentration). A particular focus was accorded to compare the ternary and binary system including Ibuprofen and highlighting the contribution of thermal and spectral characterization techniques. The addition of polyvinylpyrrolidone (PVP K30), a low molecular weight molecule, into the binary solid dispersion (Ibuprofen/β-cyclodextrin), leads to a 1.5–2 folds increase in the drug intrinsic dissolution rate only after 10 min. This resulted from physical stabilization of amorphous Ibuprofen by reducing its molecular mobility and inhibiting its recristallization even under stress conditions (75% RH and T = 40°C for six months).

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Effect of drug-carrier interaction on the dissolution behavior of solid dispersion tablets

Pharmaceutical Development and Technology ◽

10.3109/10837450903286529 ◽

2009 ◽

Vol 15 (5) ◽

pp. 460-468 ◽

Cited By ~ 11

Author(s):

Parinda Srinarong ◽

Sander Kouwen ◽

Marinella R. Visser ◽

Wouter L. J. Hinrichs ◽

Henderik W. Frijlink

Keyword(s):

Solid Dispersion ◽

Drug Carrier ◽

Dissolution Behavior ◽

Carrier Interaction

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Solubility Enhancement of Canagliflozin by Binary and Ternary Solid Dispersion Technique

International Journal of Pharmaceutical Research ◽

10.31838/ijpr/2020.12.03.103 ◽

2020 ◽

Vol 12 (03) ◽

Keyword(s):

Solid Dispersion ◽

Solubility Enhancement ◽

Ternary Solid Dispersion ◽

Dispersion Technique

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Development and Ex-vivo Evaluation of Topiramate Mucoadhesive Nanoparticles for Intranasal Delivery

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2020.13.6.10 ◽

2020 ◽

Vol 13 (6) ◽

pp. 5250-5255

Author(s):

Ashwin Kumar Tulasi ◽

Anil Goud Kandhula ◽

Ravi Krishna Velupula

Keyword(s):

Particle Size ◽

Nasal Mucosa ◽

Intranasal Administration ◽

Ex Vivo ◽

Chemical Properties ◽

Brain Targeting ◽

Oral Tablet ◽

Promising Alternative ◽

Ex Vivo Permeation

Topiramate is a second-generation antiepileptic drug used in partial, generalized seizures as an oral tablet. Oral route of administration is most convenient but shows delayed absorption. Moreover, in emergency cases, parenteral administration is not possible as it requires medical assistance. Hence, the present study was aimed to develop topiramate mucoadhesive nanoparticles for intranasal administration using ionotropic gelation method. The developed nanoparticles were evaluated for physico-chemical properties like particle size, zeta potential, surface morphology, drug content, entrapment efficiency, in vitro drug release, mucoadhesive strength, and ex vivo permeation studies in excised porcine nasal mucosa. Optimized nanoparticle formulation (T9) was composed oil mucoadhesive agent (Chitosan 1% w/w), cross linking polymer (TPP) and topiramate 275mg, 100mg and 4% respectively. It showed particle size of 350nm, high encapsulation efficacy and strong mucoadhesive strength. In vitro drug diffusion of optimized formulation showed 95.12% release of drug after 180min. Ex-vivo permeation of drug across nasal mucosa was 88.05 % after 180min. Nasocilial toxicity studies showed optimized formulation did not damage the nasal mucosa. Thus, the intranasal administration of topiramate using chitosan can be a promising alternative for brain targeting and the treatment of epilepsy.

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Development, Pre-clinical Investigation and Histopathological Evaluation of Metronidazole Loaded Topical Formulation for Treatment of Skin Inflammatory disorders

Drug Delivery Letters ◽

10.2174/2210303110999200821123047 ◽

2020 ◽

Vol 10 ◽

Author(s):

Divya Thakur ◽

Gurpreet Kaur ◽

Sheetu Wadhwa ◽

Ashana Puri

Keyword(s):

Ex Vivo ◽

Clinical Investigation ◽

In Vivo Studies ◽

Tween 20 ◽

Inflammatory Disorders ◽

Rat Paw Edema ◽

Ex Vivo Permeation ◽

Permeation Studies ◽

Anti Inflammatory

Background: Metronidazole (MTZ) is an anti-oxidant and anti-inflammatory agent with beneficial therapeutic properties. The hydrophilic nature of molecule limits its penetration across the skin. Existing commercial formulations have limitations of inadequate drug concentration present at target site, which requires frequent administration and poor patient compliance. Objective: The aim of current study was to develop and evaluate water in oil microemulsion of Metronidazole with higher skin retention for treatment of inflammatory skin disorders. Methods: Pseudo ternary phase diagrams were used in order to select the appropriate ratio of surfactant and co-surfactant and identify the microemulsion area. The selected formulation consisted of Capmul MCM as oil, Tween 20 and Span 20 as surfactant and co-surfactant, respectively, and water. The formulation was characterized and evaluated for stability, Ex vivo permeation studies and in vivo anti-inflammatory effect (carrageenan induced rat paw edema, air pouch model), anti-psoriatic activity (mouse-tail test). Results: The particle size analyses revealed average diameter and polydispersity index of selected formulation to be 16 nm and 0.373, respectively. The results of ex vivo permeation studies showed statistically higher mean cumulative amount of MTZ retained in rat skin from microemulsion i.e. 21.90 ± 1.92 μg/cm2 which was 6.65 times higher as compared to Marketed gel (Metrogyl gel®) with 3.29 ± 0.11 μg/cm2 (p<0.05). The results of in vivo studies suggested the microemulsion based formulation of MTZ to be similar in efficacy to Metrogyl gel®. Conclusion: Research suggests efficacy of the developed MTZ loaded microemulsion in treatment of chronic skin inflammatory disorders.

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