A Review on Solubility Enhancement of Carvedilol—a BCS Class II Drug

Gasper J. Fernandes, Lalit Kumar, Kartik Sharma, Rupa Tunge, Mahalaxmi Rathnanand

Research output: Contribution to journalReview article

3 Citations (Scopus)

Abstract

Purpose: Carvedilol is a third generation non-cardioselective β-blocker used in the treatment of hypertension and demonstrated a potential in the treatment of cardiovascular diseases such as myocardial infarction and arrhythmias. For any drug to be therapeutically effective, it must enter the systemic circulation and to do so, it should have an optimum aqueous solubility at the site of absorption which is a major hurdle to overcome by a formulation scientist. Carvedilol belongs to BCS (biopharmaceutical classification system) class II drugs, thus having low solubility and poor bioavailability (around 25%). Hence, the purpose of this review is to elaborate on several approaches to increase the solubility, dissolution, and bioavailability of carvedilol. Methods: Micronization, solid dispersions, cyclodextrin inclusion complex, hydrotropy, nanoformulation which include nanocrystals, nanosuspension, nanoemulsions, dendrimers, and polymeric nanoparticles. It also includes methods that have not been used on carvedilol such as cocrystallization and coamorphous technology. Results: Several approaches have successfully increased solubility and bioavailability of carvedilol and several other unexplored methods which have the potential to improve the aqueous solubility of carvedilol but have not been applied till date have also been discussed in the review. Conclusion: There are various approaches explored to increase the solubility of carvedilol with every technique having certain advantages and drawbacks. Micronization and nanoformulations (dendrimers, nanoemulsion, nanosuspension, nanocrystals, polymeric nanoparticles) are the most widely used technique for solubility enhancement of carvedilol on laboratory scale due to higher solubility and dissolution rate but they have poor industrial applicability due to difficulty in scale-up and low yield. Efforts are being made to carry out different solubility enhancement techniques with good industrial applicability for carvedilol, e.g., cocrystals. Cocrystals and coamorphous approach for poorly soluble drugs having similar properties to carvedilol have shown good solubility, dissolution, and bioavailability compared to few techniques discussed in this review, and are being widely explored to overcome the drawbacks associated with its method of preparation by carrying out certain advancements (e.g., hot melt extrusion and sonocrystallization) to produce carvedilol cocrystals and coamorphous compound with unique properties in future development.

Original languageEnglish
Pages (from-to)197-212
Number of pages16
JournalJournal of Pharmaceutical Innovation
Volume13
Issue number3
DOIs
Publication statusPublished - 01-09-2018

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Solubility
Pharmaceutical Preparations
Nanoparticles
Biological Availability
Dendrimers
carvedilol
Cyclodextrins
Cardiac Arrhythmias
Cardiovascular Diseases
Myocardial Infarction
Hypertension
Technology
Therapeutics

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science
  • Drug Discovery

Cite this

Fernandes, Gasper J. ; Kumar, Lalit ; Sharma, Kartik ; Tunge, Rupa ; Rathnanand, Mahalaxmi. / A Review on Solubility Enhancement of Carvedilol—a BCS Class II Drug. In: Journal of Pharmaceutical Innovation. 2018 ; Vol. 13, No. 3. pp. 197-212.
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abstract = "Purpose: Carvedilol is a third generation non-cardioselective β-blocker used in the treatment of hypertension and demonstrated a potential in the treatment of cardiovascular diseases such as myocardial infarction and arrhythmias. For any drug to be therapeutically effective, it must enter the systemic circulation and to do so, it should have an optimum aqueous solubility at the site of absorption which is a major hurdle to overcome by a formulation scientist. Carvedilol belongs to BCS (biopharmaceutical classification system) class II drugs, thus having low solubility and poor bioavailability (around 25{\%}). Hence, the purpose of this review is to elaborate on several approaches to increase the solubility, dissolution, and bioavailability of carvedilol. Methods: Micronization, solid dispersions, cyclodextrin inclusion complex, hydrotropy, nanoformulation which include nanocrystals, nanosuspension, nanoemulsions, dendrimers, and polymeric nanoparticles. It also includes methods that have not been used on carvedilol such as cocrystallization and coamorphous technology. Results: Several approaches have successfully increased solubility and bioavailability of carvedilol and several other unexplored methods which have the potential to improve the aqueous solubility of carvedilol but have not been applied till date have also been discussed in the review. Conclusion: There are various approaches explored to increase the solubility of carvedilol with every technique having certain advantages and drawbacks. Micronization and nanoformulations (dendrimers, nanoemulsion, nanosuspension, nanocrystals, polymeric nanoparticles) are the most widely used technique for solubility enhancement of carvedilol on laboratory scale due to higher solubility and dissolution rate but they have poor industrial applicability due to difficulty in scale-up and low yield. Efforts are being made to carry out different solubility enhancement techniques with good industrial applicability for carvedilol, e.g., cocrystals. Cocrystals and coamorphous approach for poorly soluble drugs having similar properties to carvedilol have shown good solubility, dissolution, and bioavailability compared to few techniques discussed in this review, and are being widely explored to overcome the drawbacks associated with its method of preparation by carrying out certain advancements (e.g., hot melt extrusion and sonocrystallization) to produce carvedilol cocrystals and coamorphous compound with unique properties in future development.",
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A Review on Solubility Enhancement of Carvedilol—a BCS Class II Drug. / Fernandes, Gasper J.; Kumar, Lalit; Sharma, Kartik; Tunge, Rupa; Rathnanand, Mahalaxmi.

In: Journal of Pharmaceutical Innovation, Vol. 13, No. 3, 01.09.2018, p. 197-212.

Research output: Contribution to journalReview article

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AU - Fernandes, Gasper J.

AU - Kumar, Lalit

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AU - Rathnanand, Mahalaxmi

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N2 - Purpose: Carvedilol is a third generation non-cardioselective β-blocker used in the treatment of hypertension and demonstrated a potential in the treatment of cardiovascular diseases such as myocardial infarction and arrhythmias. For any drug to be therapeutically effective, it must enter the systemic circulation and to do so, it should have an optimum aqueous solubility at the site of absorption which is a major hurdle to overcome by a formulation scientist. Carvedilol belongs to BCS (biopharmaceutical classification system) class II drugs, thus having low solubility and poor bioavailability (around 25%). Hence, the purpose of this review is to elaborate on several approaches to increase the solubility, dissolution, and bioavailability of carvedilol. Methods: Micronization, solid dispersions, cyclodextrin inclusion complex, hydrotropy, nanoformulation which include nanocrystals, nanosuspension, nanoemulsions, dendrimers, and polymeric nanoparticles. It also includes methods that have not been used on carvedilol such as cocrystallization and coamorphous technology. Results: Several approaches have successfully increased solubility and bioavailability of carvedilol and several other unexplored methods which have the potential to improve the aqueous solubility of carvedilol but have not been applied till date have also been discussed in the review. Conclusion: There are various approaches explored to increase the solubility of carvedilol with every technique having certain advantages and drawbacks. Micronization and nanoformulations (dendrimers, nanoemulsion, nanosuspension, nanocrystals, polymeric nanoparticles) are the most widely used technique for solubility enhancement of carvedilol on laboratory scale due to higher solubility and dissolution rate but they have poor industrial applicability due to difficulty in scale-up and low yield. Efforts are being made to carry out different solubility enhancement techniques with good industrial applicability for carvedilol, e.g., cocrystals. Cocrystals and coamorphous approach for poorly soluble drugs having similar properties to carvedilol have shown good solubility, dissolution, and bioavailability compared to few techniques discussed in this review, and are being widely explored to overcome the drawbacks associated with its method of preparation by carrying out certain advancements (e.g., hot melt extrusion and sonocrystallization) to produce carvedilol cocrystals and coamorphous compound with unique properties in future development.

AB - Purpose: Carvedilol is a third generation non-cardioselective β-blocker used in the treatment of hypertension and demonstrated a potential in the treatment of cardiovascular diseases such as myocardial infarction and arrhythmias. For any drug to be therapeutically effective, it must enter the systemic circulation and to do so, it should have an optimum aqueous solubility at the site of absorption which is a major hurdle to overcome by a formulation scientist. Carvedilol belongs to BCS (biopharmaceutical classification system) class II drugs, thus having low solubility and poor bioavailability (around 25%). Hence, the purpose of this review is to elaborate on several approaches to increase the solubility, dissolution, and bioavailability of carvedilol. Methods: Micronization, solid dispersions, cyclodextrin inclusion complex, hydrotropy, nanoformulation which include nanocrystals, nanosuspension, nanoemulsions, dendrimers, and polymeric nanoparticles. It also includes methods that have not been used on carvedilol such as cocrystallization and coamorphous technology. Results: Several approaches have successfully increased solubility and bioavailability of carvedilol and several other unexplored methods which have the potential to improve the aqueous solubility of carvedilol but have not been applied till date have also been discussed in the review. Conclusion: There are various approaches explored to increase the solubility of carvedilol with every technique having certain advantages and drawbacks. Micronization and nanoformulations (dendrimers, nanoemulsion, nanosuspension, nanocrystals, polymeric nanoparticles) are the most widely used technique for solubility enhancement of carvedilol on laboratory scale due to higher solubility and dissolution rate but they have poor industrial applicability due to difficulty in scale-up and low yield. Efforts are being made to carry out different solubility enhancement techniques with good industrial applicability for carvedilol, e.g., cocrystals. Cocrystals and coamorphous approach for poorly soluble drugs having similar properties to carvedilol have shown good solubility, dissolution, and bioavailability compared to few techniques discussed in this review, and are being widely explored to overcome the drawbacks associated with its method of preparation by carrying out certain advancements (e.g., hot melt extrusion and sonocrystallization) to produce carvedilol cocrystals and coamorphous compound with unique properties in future development.

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