scholarly journals The Role of Functional Excipients in Solid Oral Dosage Forms to Overcome Poor Drug Dissolution and Bioavailability

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 393 ◽  
Author(s):  
Jannes van der Merwe ◽  
Jan Steenekamp ◽  
Dewald Steyn ◽  
Josias Hamman
Keyword(s):  
Dissolution Rate ◽  
Solid Dispersions ◽  
Aqueous Solubility ◽  
Dosage Forms ◽  
Oral Dosage ◽  
Drug Dissolution ◽  
Specific Reference ◽  
Dissolution Rates ◽  
Bioavailability Enhancement ◽  
Poor Solubility

Many active pharmaceutical ingredients (APIs) exhibit poor solubility and low dissolution rates in aqueous environments such as the luminal fluids of the gastrointestinal tract. The oral bioavailability of these compounds is usually very low as a result of their poor solubility properties. In order to improve the bioavailability of these poorly soluble drugs, formulation strategies have been applied as a means to improve their aqueous solubility and dissolution rates. With respect to formulation approaches, excipients can be incorporated in the formulation to assist in the dissolution process of the drug, or specialized dosage forms can be formulated that improve dissolution rate through various mechanisms. This paper provides an overview of selected excipients (e.g., alkalinizing agents, surfactants and sugars) that can be used in formulations to increase the dissolution rate as well as specialized dosage forms such as self-emulsifying delivery systems and formulation techniques such as inclusion complexes and solid dispersions. These formulation approaches are discussed with available examples with specific reference to positive outcomes in terms of drug solubility and bioavailability enhancement.

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.

Enhancement of Solubility and Dissolution Rate of Poorly Water Soluble Drug using Cosolvency and Solid Dispersion Techniques

1970 ◽  
Vol 1 (4) ◽  
pp. 349-356
Author(s):  
Meka Lingam ◽  
Vobalaboina Venkateswarlu
Keyword(s):  
Dissolution Rate ◽  
Solid Dispersions ◽  
Physicochemical Characterization ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
Scanning Calorimetry ◽  
Peg 400 ◽  
Water Soluble Drug ◽  
Poorly Water Soluble ◽  
Poorly Water Soluble Drug

The low aqueous solubility of celecoxib (CB) and thus its low bioavailability is a problem.    Thus, it is suggested to improve the solubility using cosolvency and solid dispersions techniques. Pure CB has solubility of 6.26±0.23µg/ml in water but increased solubility of CB was observed with increasing concentration of cosolvents like PEG 400, ethanol and propylene glycol. Highest solubility (791.06±15.57mg/ml) was observed with cosolvency technique containing the mixture of composition 10:80:10%v/v of water: PEG 400: ethanol. SDs with different polymers like PVP, PEG were prepared and subjected to physicochemical characterization using Fourier-transform infrared (FTIR) spectroscopy, X-ray diffractometry (XRD), differential scanning calorimetry (DSC), solubility and dissolution studies. These studies reveals that CB exists mainly in amorphous form in prepared solid dispersions of PVP, PEG4000 and PEG6000 further it can also be confirmed by solubility and dissolution rate studies. Solid dispersions of PV5 and PV9 have shown highest saturation solubility and dissolution rate

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

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>

scholarly journals Enrichment of aqueous solubility and dissolution profile of mesalamine: In vitro evaluation of solid dispersion

2021 ◽  
Vol 9 (2) ◽  
pp. 127-135
Author(s):  
Anil Raosaheb Pawar ◽  
Pralhad Vitthalrao Mundhe ◽  
Vinayak Kashinath Deshmukh ◽  
Ramdas Bhanudas Pandhare ◽  
Tanaji Dilip Nandgude
Keyword(s):  
Ulcerative Colitis ◽  
Drug Release ◽  
Dissolution Rate ◽  
Solid Dispersion ◽  
Solid Dispersions ◽  
Aqueous Solubility ◽  
In Vitro Dissolution ◽  
Dissolution Profile ◽  
Peg 4000

The aim of the present study was to formulate solid dispersion (SD) of Mesalamine to enrich the aqueous solubility and dissolution rate. Mesalamine is used in the management of acute ulcerative colitis and for the prevention of relapse of active ulcerative colitis. In the present study, Solid dispersion of Mesalamine was prepared by Fusion and Solvent evaporation method with different polymers. SD’s were characterized by % practical yield, drug content, Solubility, FT-IR, PXRD (Powder X- ray diffractometry), SEM (Scanning electron microscopy), in vitro dissolution studies and Stability studies. The percent drug release of prepared solid dispersion of Mesalamine by fusion and solid dispersion method (FM47, FM67, SE47 and SE67) in 1:7 ratio was found 81.36±0.41, 86.29±0.64, 82.45±0.57and 87.25±1.14 respectively. The aqueous solubility and percent drug release of solid dispersion of Mesalamine by both methods was significantly increased. The PXRD demonstrated that there was a significant decrease in crystallinity of pure drug present in the solid dispersions, which resulted in an increased aqueous solubility and dissolution rate of Mesalamine.The significant increase in aqueous solubility and dissolution rate of Mesalamine was observed in solid dispersion as the crystallinity of the drug decreased, absence of aggregation and agglomeration, increased wetability and good dispersibility after addition of PEG 4000 and PEG 6000.

Fusion as an Approach to Enhance Dissolution Rate of a Poorly Water-Soluble Drug (Curcurmin)

2011 ◽  
Vol 393-395 ◽  
pp. 119-122
Author(s):  
Dong Hua Wan ◽  
Fen Lin ◽  
Qu Xiang Liao
Keyword(s):  
Dissolution Rate ◽  
Drug Loading ◽  
Solid Dispersions ◽  
Gastric Fluid ◽  
Molecular State ◽  
Water Soluble ◽  
Drug Dissolution ◽  
Simulated Gastric Fluid ◽  
Scanning Calorimetry ◽  
Rate Improvement

It’s well known that curcumin is practically insoluble in water. Therefore, to improve the drug dissolution rate, fusion approach was employed to prepare curcumin solid dispersions (SDs) in the carrier Pluronic F68 with three different drug loads. The dissolution rate of curcumin from the SDs was measured at simulated gastric fluid. The concentration of the dissolved drug in the medium was determined by HPLC. The dissolution rates of the formulations were dependent on the drug loading in SDs. 92.2% CUR was dissolved in 10 min from the SDs with 8.97% drug load, whereas the amounts of drug released were 65.8% and 84.2% within 120 min from the SDs with 18.9% and 29.0% drug loads, respectively. The Fourier transform infrared spectra indicated hydrogen bond between the drug and carrier. Furthermore, their physicochemical properties were well investigated using differential scanning calorimetry and X-ray diffraction. In the dispersions containing 8.97% CUR, the drug was in the molecular state. At a composition of approximately 18.9%, CUR was dispersed as micro-fine crystals. These interesting results indicate that the physical states of the drug in the carrier, which are governed by the drug loading, can affect the dissolution rate improvement.

scholarly journals Agglomerated Oral Dosage Forms of Artemisinin/β-Cyclodextrin Spray-Dried Primary Microparticles Showing Increased Dissolution Rate and Bioavailability

2013 ◽  
Vol 14 (3) ◽  
pp. 911-918 ◽  
Author(s):  
Anna Giulia Balducci ◽  
Enrico Magosso ◽  
Gaia Colombo ◽  
Fabio Sonvico ◽  
Nurzalina Abdul Karim Khan ◽  
...  
Keyword(s):  
Dissolution Rate ◽  
Dosage Forms ◽  
Oral Dosage ◽  
Oral Dosage Forms ◽  
Spray Dried

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

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>

scholarly journals Hot-melt extrusion and prilling as contemporary and promising techniques in the solvent free production of solid oral dosage forms, based on solid dispersions

2016 ◽  
Vol 62 (1) ◽  
pp. 3-24 ◽  
Author(s):  
Aleksandar Aleksovski ◽  
Chris Vervaet ◽  
Rok Dreu
Keyword(s):  
Drug Delivery ◽  
Hot Melt Extrusion ◽  
Dosage Forms ◽  
Solvent Free ◽  
Oral Dosage ◽  
Drug Dissolution ◽  
Melt Extrusion ◽  
Solid Oral Dosage Forms ◽  
Oral Dosage Forms ◽  
Hot Melt

Hot melt extrusion and prilling are gaining importance as solvent free and continuous techniques in the production of solid oral dosage forms with added value, by incorporating active compound in a molten carrier which is further solidified to form solid dispersion. This article reviews these two techniques in terms of understanding process basics, equipment characteristics, required properties of processed materials and application of the processes for development of solid oral dosage forms. Studies revealed that both hot-melt extrusion and prilling are regarded as simple, robust and continuous methods for processing different types of materials and production of solid dosage forms based on solid matrices. However, understanding of their concepts and requirements together with careful material selection is crucial for stable material processing and obtaining stable products of high-quality. Hot-melt extrusion proved to be a suitable method for production of modified release dosage forms, taste masked dosage forms and dosage forms offering improved drug dissolution rate and solubility. Prilling till now has been successfully applied just in the production of multiple unit drug delivery systems for immediate and sustained drug delivery. Further studies on product development and process understanding are required for full implementation of prilling in the pharmaceutical field.

scholarly journals EFFECT OF CARRIER TYPES ON THE PHYSICOCHEMICAL AND DISSOLUTION CHARACTERISTICS OF OFLOXACIN SOLID DISPERSION

2002 ◽  
Vol 70 (3) ◽  
pp. 309-316
Author(s):  
Okonogi S ◽  
Sirithunyalung J ◽  
Sirithunyalig B ◽  
Wolschann P ◽  
Viernstein H
Keyword(s):  
Dissolution Rate ◽  
Solid Dispersion ◽  
Solid Dispersions ◽  
Weight Fraction ◽  
Water Soluble ◽  
Drug Dissolution ◽  
Dissolution Enhancement ◽  
Water Soluble Polymers ◽  
Dissolution Properties ◽  
Peg 4000

Solid dispersions of ofloxacin (OFX) and of a number of carriers including chitosan and the water soluble polymers polyethylene glycol (PEG) 4000, PEG 20000, and polyvinylpyrrolidone K- 90 were prepared by solvent evaporation method in order to increase the dissolution of the drug. The solid dispersions were subjected to X-ray diffraction, DSC, and dissolution to characterize their physicochemical and dissolution properties. The results demonstrated a decrease in drug crystallinity at higher amounts of carrier. Dissolution studies indicated that the dissolution rate of OFX was markedly increased in these solid dispersion systems compared with the pure drug. The results also showed that the increase in dissolution rate was higher when the weight fraction of carriers increased. An influence of molecular weight of PEG on OFX dissolution could also be observed. In solid dispersion with 1:9 ratio drug to carrier, PEG 4000 gave highest drug dissolution rate, whereas in 1:1 ratio, chitosan seems to be the best carrier for drug release. It was concluded that chitosan might be the carrier of choice for dissolution enhancement in solid dispersions with high content of drug.

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