Pub Date : 2014-02-21DOI: 10.2174/1874126601405010001
S. Chakraborty, Kavan Pandya, D. Aggarwal
The present study was aimed to establish prospective IVIVC method for generic products using example of two different drug formulations (aprepitant capsules, immediate release and donepezil tablets, sustained release). The in vitro dissolution of these formulations was examined by using USP-II apparatus and different range of dissolution media. The dissolution profile was matched with the deconvoluted profile of drugs obtained from literature data to select biorelevant dissolution media. An IVIVC was established by using the mean fraction dissolved (FD) and mean fraction absorbed (FA) and used to simulate the plasma profile of these formulations by convolution from optimized dissolution media. The in vivo drug disposition was studied in an open label, balanced, randomized, single dose, two way crossover study in healthy subjects. Predicted PK parameters were compared with observed parameters. A positive correlation was seen between the FD and FA for both formulations with r 2 =0.989 for aprepitant and r 2 =0.995 for donepezil. The percent prediction error for both C max and AUC t were ≤15% while predicting the plasma concentration time profile for human bioequivalence studies for these formulations. Results supports use of prospective method in establishing IVIVC while predicting in vivo pharmacokinetic profile for bioequivalence studies for generic product development.
{"title":"Establishing Prospective IVIVC for Generic Pharmaceuticals: Methodologies Assessment","authors":"S. Chakraborty, Kavan Pandya, D. Aggarwal","doi":"10.2174/1874126601405010001","DOIUrl":"https://doi.org/10.2174/1874126601405010001","url":null,"abstract":"The present study was aimed to establish prospective IVIVC method for generic products using example of two different drug formulations (aprepitant capsules, immediate release and donepezil tablets, sustained release). The in vitro dissolution of these formulations was examined by using USP-II apparatus and different range of dissolution media. The dissolution profile was matched with the deconvoluted profile of drugs obtained from literature data to select biorelevant dissolution media. An IVIVC was established by using the mean fraction dissolved (FD) and mean fraction absorbed (FA) and used to simulate the plasma profile of these formulations by convolution from optimized dissolution media. The in vivo drug disposition was studied in an open label, balanced, randomized, single dose, two way crossover study in healthy subjects. Predicted PK parameters were compared with observed parameters. A positive correlation was seen between the FD and FA for both formulations with r 2 =0.989 for aprepitant and r 2 =0.995 for donepezil. The percent prediction error for both C max and AUC t were ≤15% while predicting the plasma concentration time profile for human bioequivalence studies for these formulations. Results supports use of prospective method in establishing IVIVC while predicting in vivo pharmacokinetic profile for bioequivalence studies for generic product development.","PeriodicalId":421840,"journal":{"name":"The Open Drug Delivery Journal","volume":"01 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2014-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131133515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-08-24DOI: 10.2174/1874126601004010055
Margherita Vono, D. Cosco, C. Celia, D. Paolino, M. Celano, D. Russo, M. Fresta
Papillary carcinoma is the most common form of malignant thyroid tumor. At present, a subset of these tumors are poorly responsive to the current treatment. Gemcitabine is a pyrimidine analog active against different types of solid tumors, but its use is limited by its short half-life. To improve the therapeutic effectiveness of this drug, gemcitabine- loaded unilamellar pegylated liposomes were prepared and investigated against two human papillary thyroid carcinoma cell lines, i.e. TPC-1 and B-CPAP cells. The pH gradient drug encapsulation followed by the membrane extrusion technique were used to achieve unilamellar liposomes characterized by a mean size of ~200 nm, a polydispersity index of 0.02 and a zeta potential of -1.7 mV. The gemcitabine was released from liposomes following a biphasic profile. The liposomal encapsulated gemcitabine showed an increased cytotoxic activity compared to the free drug against both thyroid carcinoma cell lines, as a consequence of the better drug internalization favored by the vesicular device. These findings demonstrate the advantage of channeling gemcitabine by liposomes suggesting a promising role for such a pharmaceutical formulation in the treatment of refractory papillary thyroid carcinoma.
{"title":"In Vitro Evaluation of the Activity of Gemcitabine-Loaded Pegylated Unilamellar Liposomes Against Papillary Thyroid Cancer Cells","authors":"Margherita Vono, D. Cosco, C. Celia, D. Paolino, M. Celano, D. Russo, M. Fresta","doi":"10.2174/1874126601004010055","DOIUrl":"https://doi.org/10.2174/1874126601004010055","url":null,"abstract":"Papillary carcinoma is the most common form of malignant thyroid tumor. At present, a subset of these tumors are poorly responsive to the current treatment. Gemcitabine is a pyrimidine analog active against different types of solid tumors, but its use is limited by its short half-life. To improve the therapeutic effectiveness of this drug, gemcitabine- loaded unilamellar pegylated liposomes were prepared and investigated against two human papillary thyroid carcinoma cell lines, i.e. TPC-1 and B-CPAP cells. The pH gradient drug encapsulation followed by the membrane extrusion technique were used to achieve unilamellar liposomes characterized by a mean size of ~200 nm, a polydispersity index of 0.02 and a zeta potential of -1.7 mV. The gemcitabine was released from liposomes following a biphasic profile. The liposomal encapsulated gemcitabine showed an increased cytotoxic activity compared to the free drug against both thyroid carcinoma cell lines, as a consequence of the better drug internalization favored by the vesicular device. These findings demonstrate the advantage of channeling gemcitabine by liposomes suggesting a promising role for such a pharmaceutical formulation in the treatment of refractory papillary thyroid carcinoma.","PeriodicalId":421840,"journal":{"name":"The Open Drug Delivery Journal","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2010-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133931220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-05-20DOI: 10.2174/1874126601004020038
S. Qureshi
{"title":"In Vitro-In Vivo Correlation (IVIVC) and Determining Drug Concentrations in Blood from Dissolution Testing A Simple and Practical Approach~!2009-10-30~!2010-01-04~!2010-04-29~!","authors":"S. Qureshi","doi":"10.2174/1874126601004020038","DOIUrl":"https://doi.org/10.2174/1874126601004020038","url":null,"abstract":"","PeriodicalId":421840,"journal":{"name":"The Open Drug Delivery Journal","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2010-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116161021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-05-20DOI: 10.2174/1874126601004010001
S. Qureshi
{"title":"Hot Topic: [Drug Dissolution Testing (Guest Editor: Dr. Saeed A. Qureshi)]","authors":"S. Qureshi","doi":"10.2174/1874126601004010001","DOIUrl":"https://doi.org/10.2174/1874126601004010001","url":null,"abstract":"","PeriodicalId":421840,"journal":{"name":"The Open Drug Delivery Journal","volume":"25 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2010-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116553220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-05-20DOI: 10.2174/1874126601004020002
N. Fotaki, M. Vertzoni
{"title":"Biorelevant Dissolution Methods and Their Applications in In Vitro- In Vivo Correlations for Oral Formulations~!2009-09-14~!2009-11-02~!2010-04-29~!","authors":"N. Fotaki, M. Vertzoni","doi":"10.2174/1874126601004020002","DOIUrl":"https://doi.org/10.2174/1874126601004020002","url":null,"abstract":"","PeriodicalId":421840,"journal":{"name":"The Open Drug Delivery Journal","volume":"84 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2010-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124976471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-04-29DOI: 10.2174/1874126601004020021
Rajesh Vadlapatla, E. Fifer, Cherng-ju Kim
In situ drug and organic electrolyte complex tablets were investigated as extended release dosage forms. Incor- porating a 1:1 molar ratio of diltiazem HCl and an anionic organic electrolyte (i.e., Na deoxycholate) into HPC tablets ex- tended the total release time with a near zero - order release rate (release exponent, n = 0.85 - 0.97) due to in situ complex formation of the drug and the organic electrolyte. When the molar ratio was less than 1 (e.g., 0.5), drug release was faster and the effect of drug diffusion was only slightly observable with n = 0.82 due to the availability of uncomplexed free drug to diffuse out of the swollen HPC gel layer. Little effect was observed for the type of amine in the drug or drug solu- bility on release kinetics for diltiazem HCl, verapamil HCl, and propranolol HCl. Benzathine diacetate was used as the or- ganic electrolyte, in situ complexing agent for anionic drugs (e.g., Na salicylate). Even though the total extended release time was increased from 500 min to 1600 min, drug release kinetics for the in situ salicylate benzathine complex HPC tab- lets (n = 0.54 - 0.59) was not much improved compared to those of Na salicylate HPC tablets (0.40 - 0.41). Anionic drugs with low solubility (e.g., naproxen Na and tolmetin Na) showed slightly sigmoidal release profiles with n = 1.09 and 1.13, respectively. No difference in release kinetics among different cationic organic electrolytes (e.g., benzathine diacetate, aminodiphenylmethane HCl, and N-benzyl-2-phenethylamine HCl) for Na salicylate was found. It was found that more linear release kinetics was obtained when organic electrolytes were present in tablets more than the amount required to form 1:1 complexes with oppositely charged drugs.
{"title":"In Situ Complex Systems of Drug and Organic Electrolyte for Extended Release Tablets Using HPC","authors":"Rajesh Vadlapatla, E. Fifer, Cherng-ju Kim","doi":"10.2174/1874126601004020021","DOIUrl":"https://doi.org/10.2174/1874126601004020021","url":null,"abstract":"In situ drug and organic electrolyte complex tablets were investigated as extended release dosage forms. Incor- porating a 1:1 molar ratio of diltiazem HCl and an anionic organic electrolyte (i.e., Na deoxycholate) into HPC tablets ex- tended the total release time with a near zero - order release rate (release exponent, n = 0.85 - 0.97) due to in situ complex formation of the drug and the organic electrolyte. When the molar ratio was less than 1 (e.g., 0.5), drug release was faster and the effect of drug diffusion was only slightly observable with n = 0.82 due to the availability of uncomplexed free drug to diffuse out of the swollen HPC gel layer. Little effect was observed for the type of amine in the drug or drug solu- bility on release kinetics for diltiazem HCl, verapamil HCl, and propranolol HCl. Benzathine diacetate was used as the or- ganic electrolyte, in situ complexing agent for anionic drugs (e.g., Na salicylate). Even though the total extended release time was increased from 500 min to 1600 min, drug release kinetics for the in situ salicylate benzathine complex HPC tab- lets (n = 0.54 - 0.59) was not much improved compared to those of Na salicylate HPC tablets (0.40 - 0.41). Anionic drugs with low solubility (e.g., naproxen Na and tolmetin Na) showed slightly sigmoidal release profiles with n = 1.09 and 1.13, respectively. No difference in release kinetics among different cationic organic electrolytes (e.g., benzathine diacetate, aminodiphenylmethane HCl, and N-benzyl-2-phenethylamine HCl) for Na salicylate was found. It was found that more linear release kinetics was obtained when organic electrolytes were present in tablets more than the amount required to form 1:1 complexes with oppositely charged drugs.","PeriodicalId":421840,"journal":{"name":"The Open Drug Delivery Journal","volume":"170 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2010-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134233402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-04-29DOI: 10.2174/1874126601004020014
T. Moore, M. Long, William A. Kentrup, M. Oates, Cheryl Kelley, Stephen P Sojkowski
This guidance is intended to serve as a companion document for ASTM Standard E 2503-07, "Standard Prac- tice for Qualification of Basket and Paddle Dissolution Apparatus", by providing practical information useful for the im- plementation of mechanical calibration. Particular focus is placed on use of the available tools to make the required meas- urements.
{"title":"Implementation Guidance for American Society for Testing and Materials (ASTM) E 2503-07 \"Standard Practice for Qualification of Basket and Paddle Dissolution Apparatus\"","authors":"T. Moore, M. Long, William A. Kentrup, M. Oates, Cheryl Kelley, Stephen P Sojkowski","doi":"10.2174/1874126601004020014","DOIUrl":"https://doi.org/10.2174/1874126601004020014","url":null,"abstract":"This guidance is intended to serve as a companion document for ASTM Standard E 2503-07, \"Standard Prac- tice for Qualification of Basket and Paddle Dissolution Apparatus\", by providing practical information useful for the im- plementation of mechanical calibration. Particular focus is placed on use of the available tools to make the required meas- urements.","PeriodicalId":421840,"journal":{"name":"The Open Drug Delivery Journal","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2010-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122114470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-04-29DOI: 10.2174/1874126601004020048
Bashar A. Alkhalidi, Hatim S Alkhatib, Ayman Khdair
Drug dissolution studies are commonly conducted using compendial methods employing USP Paddle and Basket apparatuses. In many cases, dissolution studies can be of limited benefit especially for product-dependent dissolu- tion procedures like in extended release (ER) formulations. The high variability in dissolution testing, that is not product- related, emphasizes the need for developing new methods for dissolution testing that can address the artifacts found with the current USP dissolution methods. A crescent shaped spindle was suggested as a solution to overcome drawbacks associated with conventional dissolution methods. Diltiazem immediate- and extended-release tablets and capsules were used to evaluate the crescent-shaped spindle and compare it to the USP paddle system. Appropriate dissolution rates were obtained using crescent-shaped spindle at 25 rpm compared to higher rotation speeds of 75/100 rpm with the USP Paddle. Similarity factor (F2) and dissolution efficiency (DE) parameters were used to evaluate dissolution profiles. Statistical analysis using student t-test and P-value was used to compare the results under various test conditions. For the immediate release (IR) products, only one product out of four had similar dissolution profile in the USP paddle and Crescent shaped spindles. Two products out of five ER products were found similar based on the F2 value. In general, Crescent shaped spindle provided better evaluation for the dissolution of IR and ER products without any evidence of harsh stirring environment or crushing.
{"title":"Comparative Dissolution of Diltiazem Immediate and Extended Release Products Using Conventional USP and Innovative Dissolution Paddles","authors":"Bashar A. Alkhalidi, Hatim S Alkhatib, Ayman Khdair","doi":"10.2174/1874126601004020048","DOIUrl":"https://doi.org/10.2174/1874126601004020048","url":null,"abstract":"Drug dissolution studies are commonly conducted using compendial methods employing USP Paddle and Basket apparatuses. In many cases, dissolution studies can be of limited benefit especially for product-dependent dissolu- tion procedures like in extended release (ER) formulations. The high variability in dissolution testing, that is not product- related, emphasizes the need for developing new methods for dissolution testing that can address the artifacts found with the current USP dissolution methods. A crescent shaped spindle was suggested as a solution to overcome drawbacks associated with conventional dissolution methods. Diltiazem immediate- and extended-release tablets and capsules were used to evaluate the crescent-shaped spindle and compare it to the USP paddle system. Appropriate dissolution rates were obtained using crescent-shaped spindle at 25 rpm compared to higher rotation speeds of 75/100 rpm with the USP Paddle. Similarity factor (F2) and dissolution efficiency (DE) parameters were used to evaluate dissolution profiles. Statistical analysis using student t-test and P-value was used to compare the results under various test conditions. For the immediate release (IR) products, only one product out of four had similar dissolution profile in the USP paddle and Crescent shaped spindles. Two products out of five ER products were found similar based on the F2 value. In general, Crescent shaped spindle provided better evaluation for the dissolution of IR and ER products without any evidence of harsh stirring environment or crushing.","PeriodicalId":421840,"journal":{"name":"The Open Drug Delivery Journal","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2010-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116894468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-04-29DOI: 10.2174/1874126601004010002
N. Fotaki, M. Vertzoni
Dissolution tests that can predict the in vivo performance of drug products are usually called biorelevant dissolution tests. Biorelevant dissolution testing can be used to guide formulation development, to identify food effects on the dissolution and bioavailability of orally administered drugs, and to identify solubility limitations and stability issues. To develop a biorelevant dissolution test for oral dosage forms, the physiological conditions in the gastrointestinal (GI) tract that can affect drug dissolution are taken into consideration according to the properties of the drug and dosage form. A variety of biorelevant methods in terms of media and hydrodynamics to simulate the contents and the conditions of the GI tract are presented. The ability of biorelevant dissolution methods to predict in vivo performance and generate successful in vitro-in vivo correlations (IVIVC) for oral formulations are also discussed through several studies.
{"title":"Biorelevant dissolution methods and their applications in in vitroin vivo correlations for oralformulations","authors":"N. Fotaki, M. Vertzoni","doi":"10.2174/1874126601004010002","DOIUrl":"https://doi.org/10.2174/1874126601004010002","url":null,"abstract":"Dissolution tests that can predict the in vivo performance of drug products are usually called biorelevant dissolution tests. Biorelevant dissolution testing can be used to guide formulation development, to identify food effects on the dissolution and bioavailability of orally administered drugs, and to identify solubility limitations and stability issues. To develop a biorelevant dissolution test for oral dosage forms, the physiological conditions in the gastrointestinal (GI) tract that can affect drug dissolution are taken into consideration according to the properties of the drug and dosage form. A variety of biorelevant methods in terms of media and hydrodynamics to simulate the contents and the conditions of the GI tract are presented. The ability of biorelevant dissolution methods to predict in vivo performance and generate successful in vitro-in vivo correlations (IVIVC) for oral formulations are also discussed through several studies.","PeriodicalId":421840,"journal":{"name":"The Open Drug Delivery Journal","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2010-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115486727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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