Pub Date : 2019-08-31DOI: 10.2174/2210303109666190508083142
Nidhi Sachan, S. Bahadur, P. Sharma
Nasal drug delivery has been used since ancient times for therapeutic and recreational purposes. For the last decades, nasal drug delivery has been extended for drug delivery to the brain. Therefore, it is important to understand the several physiological and physicochemical factors of the nose for brain drug delivery. A major highlight of the present review article is the several aspects of the nose to brain delivery for migraine treatment. This review will help to understand different factors which are needed to be considered for intra-nasal formulations to achieve the desired therapeutic effects. There are different drug delivery routes available for migraine treatment. Nasal route of administration may be optimal for migraine treatment which has better drug concentration in the brain. These approaches may be associated with limiting the adverse effects of drug therapeutics. A list of total FDA approved approaches has been provided. Novel approaches used for drug targeting to get maximum drug concentration in the brain have been highlighted. Several novel drug delivery approaches such as nanoparticle, nanoemulsion, microspheres, etc. have been reported and better therapeutic effects have been observed. Among the novel approaches, some of them are currently under either Phase II or Phase III development but may prove to offer better clinical effects. These approaches would become the alternate choice for migraine treatment with patients experiencing symptoms consistent with gastrointestinal dysfunction associated with migraine. Intra-nasal administration of drugs for migraine treatment may offer an interesting alternative for achieving therapeutic effects of drugs which are comparable to the parenteral route. Nasal drug delivery can be an alternative route of drug administration for migraine treatment to achieve better bioavailability.
{"title":"Recent Advances and Novel Approaches for Nose to Brain Drug Delivery for Treatment of Migraine","authors":"Nidhi Sachan, S. Bahadur, P. Sharma","doi":"10.2174/2210303109666190508083142","DOIUrl":"https://doi.org/10.2174/2210303109666190508083142","url":null,"abstract":"\u0000\u0000Nasal drug delivery has been used since ancient times for therapeutic and recreational\u0000purposes. For the last decades, nasal drug delivery has been extended for drug delivery to the\u0000brain. Therefore, it is important to understand the several physiological and physicochemical factors of\u0000the nose for brain drug delivery.\u0000\u0000\u0000\u0000A major highlight of the present review article is the several aspects of the nose to brain delivery\u0000for migraine treatment. This review will help to understand different factors which are needed to\u0000be considered for intra-nasal formulations to achieve the desired therapeutic effects.\u0000\u0000\u0000\u0000There are different drug delivery routes available for migraine treatment. Nasal route of administration\u0000may be optimal for migraine treatment which has better drug concentration in the brain.\u0000These approaches may be associated with limiting the adverse effects of drug therapeutics.\u0000\u0000\u0000\u0000A list of total FDA approved approaches has been provided. Novel approaches used for drug\u0000targeting to get maximum drug concentration in the brain have been highlighted. Several novel drug\u0000delivery approaches such as nanoparticle, nanoemulsion, microspheres, etc. have been reported and better\u0000therapeutic effects have been observed. Among the novel approaches, some of them are currently\u0000under either Phase II or Phase III development but may prove to offer better clinical effects. These approaches\u0000would become the alternate choice for migraine treatment with patients experiencing symptoms\u0000consistent with gastrointestinal dysfunction associated with migraine.\u0000\u0000\u0000\u0000 Intra-nasal administration of drugs for migraine treatment may offer an interesting alternative\u0000for achieving therapeutic effects of drugs which are comparable to the parenteral route. Nasal drug\u0000delivery can be an alternative route of drug administration for migraine treatment to achieve better\u0000bioavailability.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47080795","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 : 2019-08-31DOI: 10.2174/2210303109666190401231920
A. Parashar, P. Patel, A. Gupta, N. Jain, B. Kurmi
The present study was aimed at developing and exploring the use of PEGylated Poly (propyleneimine) dendrimers for the delivery of an anti-diabetic drug, insulin.For this study, 4.0G PPI dendrimer was synthesized by successive Michael addition and exhaustive amidation reactions, using ethylenediamine as the core and acrylonitrile as the propagating agent. Two different activated PEG moieties were employed for PEGylation of PPI dendrimers. Various physicochemical and physiological parameters UV, IR, NMR, TEM, DSC, drug entrapment, drug release, hemolytic toxicity and blood glucose level studies of both PEGylated and non- PEGylated dendritic systems were determined and compared.PEGylation of PPI dendrimers caused increased solubilization of insulin in the dendritic framework as well as in PEG layers, reduced drug release and hemolytic toxicity as well as increased therapeutic efficacy with reduced side effects of insulin. These systems were found to be suitable for sustained delivery of insulin by in vitro and blood glucose-level studies in albino rats, without producing any significant hematological disturbances.Thus, surface modification of PPI dendrimers with PEG molecules has been found to be a suitable approach to utilize it as a safe and effective nano-carrier for drug delivery.
{"title":"Synthesis, Characterization andin vivoEvaluation of PEGylated PPI Dendrimer for Safe and Prolonged Delivery of Insulin","authors":"A. Parashar, P. Patel, A. Gupta, N. Jain, B. Kurmi","doi":"10.2174/2210303109666190401231920","DOIUrl":"https://doi.org/10.2174/2210303109666190401231920","url":null,"abstract":"The present study was aimed at developing and exploring the use of PEGylated Poly (propyleneimine) dendrimers for the delivery of an anti-diabetic drug, insulin.For this study, 4.0G PPI dendrimer was synthesized by successive Michael addition and exhaustive amidation reactions, using ethylenediamine as the core and acrylonitrile as the propagating agent. Two different activated PEG moieties were employed for PEGylation of PPI dendrimers. Various physicochemical and physiological parameters UV, IR, NMR, TEM, DSC, drug entrapment, drug release, hemolytic toxicity and blood glucose level studies of both PEGylated and non- PEGylated dendritic systems were determined and compared.PEGylation of PPI dendrimers caused increased solubilization of insulin in the dendritic framework as well as in PEG layers, reduced drug release and hemolytic toxicity as well as increased therapeutic efficacy with reduced side effects of insulin. These systems were found to be suitable for sustained delivery of insulin by in vitro and blood glucose-level studies in albino rats, without producing any significant hematological disturbances.Thus, surface modification of PPI dendrimers with PEG molecules has been found to be a suitable approach to utilize it as a safe and effective nano-carrier for drug delivery.","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44586237","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 : 2019-08-20DOI: 10.2174/2210303109666190226152857
S. S. Boregowda, Sadanand R. Maggidi, Rajamma A. Jayaramu, Nethravathi Puttegowda, Nikhat Parbin
The present research work is aimed at the development of an in situ gel polymer composite to provide local and sustained delivery of therapeutic agents in the vaginal cavity. Administration of medicated gel into a vaginal cavity is very complicated, inconvenient and needs expert assistance. There is a chance of expulsion of liquid formulation from site of application, leads to poor therapeutic efficacy. The effective drug delivery system for the vaginal cavity should be of liquid for application and gel to reside in the cavity. In situ gel composed of chitosan (0.8%) cross-linked with β-glycerol phosphate (15%) and glutaraldehyde treated guar gum (0.2%) was developed. Gel was characterized for in situ gelling properties. In vitro drug release pattern of the gel was tested on a nutrient agar medium containing attenuated E. coli and B. Subtilis. In vitro diffusion pattern of gel was tested using KC-diffusion cell with Simulated Vaginal Fluid (SVF) (pH 4.2) as the diffusion medium. In situ gel exhibited sharpest sol-gel transition at 35±2°C, at pH 5.4 in 62±1.31sec. The viscosity of polymer composite is 51.25±3.68 CPs at 20±2°C and 328.56±4.16 CPs at 35±2°C. The gelation time of gel was found to be decreasing as the concentration of cross-linking agent β-GP increased. Formulations exhibited a shear thinning property. Drug release from this polymeric composite was found to be highly linear and follows non-fickian diffusion mechanism. This advanced thermosensitive in situ gel is convenient to apply and reside in the vaginal cavity for a prolonged period of time. The gel is mucoadhesive, biodegradable and suitable for controlled drug delivery in the cavity.
{"title":"Development of an In situ Gel Polymer Composite for Local and Sustained Delivery of Drugs in Vaginal Cavity","authors":"S. S. Boregowda, Sadanand R. Maggidi, Rajamma A. Jayaramu, Nethravathi Puttegowda, Nikhat Parbin","doi":"10.2174/2210303109666190226152857","DOIUrl":"https://doi.org/10.2174/2210303109666190226152857","url":null,"abstract":"\u0000\u0000The present research work is aimed at the development of an in situ gel polymer\u0000composite to provide local and sustained delivery of therapeutic agents in the vaginal cavity. Administration\u0000of medicated gel into a vaginal cavity is very complicated, inconvenient and needs expert assistance.\u0000There is a chance of expulsion of liquid formulation from site of application, leads to poor therapeutic\u0000efficacy. The effective drug delivery system for the vaginal cavity should be of liquid for application\u0000and gel to reside in the cavity.\u0000\u0000\u0000\u0000In situ gel composed of chitosan (0.8%) cross-linked with β-glycerol phosphate (15%) and\u0000glutaraldehyde treated guar gum (0.2%) was developed. Gel was characterized for in situ gelling properties.\u0000In vitro drug release pattern of the gel was tested on a nutrient agar medium containing attenuated\u0000E. coli and B. Subtilis. In vitro diffusion pattern of gel was tested using KC-diffusion cell with\u0000Simulated Vaginal Fluid (SVF) (pH 4.2) as the diffusion medium.\u0000\u0000\u0000\u0000 In situ gel exhibited sharpest sol-gel transition at 35±2°C, at pH 5.4 in 62±1.31sec. The viscosity\u0000of polymer composite is 51.25±3.68 CPs at 20±2°C and 328.56±4.16 CPs at 35±2°C. The gelation\u0000time of gel was found to be decreasing as the concentration of cross-linking agent β-GP increased.\u0000Formulations exhibited a shear thinning property. Drug release from this polymeric composite was\u0000found to be highly linear and follows non-fickian diffusion mechanism.\u0000\u0000\u0000\u0000 This advanced thermosensitive in situ gel is convenient to apply and reside in the vaginal\u0000cavity for a prolonged period of time. The gel is mucoadhesive, biodegradable and suitable for controlled\u0000drug delivery in the cavity.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48334523","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 : 2019-08-20DOI: 10.2174/2210303109666190227163606
D. Divya, D Desai Namita
Adapalene is a promising third generation retinoid used in the topical treatment of acne vulgaris. However, the major drawback associated with conventional topical therapy of Adapalene is the ‘retinoid reaction’ which is dose-dependent and characterized by erythema, scaling and burning sensation at the application sites. Microparticulate drug delivery can play a major role in reducing side effects and providing better patient compliance due to targeted delivery. Adapalene microparticles were prepared using quasi emulsion solvent diffusion method. The effects of formulation variables including polymer ratios, amounts of emulsifier, drug loading and process variables such as stirring time and speed on the physical characteristics of microparticles were investigated. The developed microparticles were characterized by DSC and SEM. Adapalene microparticles were incorporated into Carbopol 971 NF gel for ease of topical delivery. Adapalene microparticulate topical gel showed sustained drug release over 8 hours in in vitro studies. The amount of drug retained in the rat skin during ex vivo studies was higher in the microparticulate topical gel (227.43 ± 0.83 µg/cm2) as compared to the marketed formulation (81.4 ± 1.11 µg/cm2) after 8 hours indicating localized and sustained drug action that can be useful in treating acne vulgaris. The safety of optimized Adapalene gel determined by skin irritation studies performed on Sprague Dawley rats showed no irritation potential. Microparticles can provide promising carrier systems to deliver Adapalene, improving patient compliance due to enhanced skin deposition, localized and sustained action with reduced associated irritant effects.
{"title":"Development and Evaluation of Particulate Microcarriers of Adapalene as a Topical Delivery System","authors":"D. Divya, D Desai Namita","doi":"10.2174/2210303109666190227163606","DOIUrl":"https://doi.org/10.2174/2210303109666190227163606","url":null,"abstract":"Adapalene is a promising third generation retinoid used in the topical treatment\u0000of acne vulgaris. However, the major drawback associated with conventional topical therapy of\u0000Adapalene is the ‘retinoid reaction’ which is dose-dependent and characterized by erythema, scaling\u0000and burning sensation at the application sites. Microparticulate drug delivery can play a major role in\u0000reducing side effects and providing better patient compliance due to targeted delivery.\u0000\u0000\u0000\u0000Adapalene microparticles were prepared using quasi emulsion solvent diffusion method. The\u0000effects of formulation variables including polymer ratios, amounts of emulsifier, drug loading and process\u0000variables such as stirring time and speed on the physical characteristics of microparticles were investigated.\u0000The developed microparticles were characterized by DSC and SEM. Adapalene microparticles\u0000were incorporated into Carbopol 971 NF gel for ease of topical delivery.\u0000\u0000\u0000\u0000Adapalene microparticulate topical gel showed sustained drug release over 8 hours in in vitro\u0000studies. The amount of drug retained in the rat skin during ex vivo studies was higher in the microparticulate\u0000topical gel (227.43 ± 0.83 µg/cm2) as compared to the marketed formulation (81.4 ±\u00001.11 µg/cm2) after 8 hours indicating localized and sustained drug action that can be useful in treating\u0000acne vulgaris. The safety of optimized Adapalene gel determined by skin irritation studies performed on\u0000Sprague Dawley rats showed no irritation potential.\u0000\u0000\u0000\u0000 Microparticles can provide promising carrier systems to deliver Adapalene, improving patient\u0000compliance due to enhanced skin deposition, localized and sustained action with reduced associated\u0000irritant effects.","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47110309","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 : 2019-08-20DOI: 10.2174/2210303109666190404143906
C. A. B. Nieva, M. Villegas, A. Cid, Analía I Romero, J. Bermudez
Chitosan (CS) is a biomaterial derived from chitin, known for its excellent biological properties. One of the most interesting features of CS is its potential for chemical derivatization, which makes it a versatile material and allows to expand its applications. In the last years, the interest on this polymer and its pharmaceutical applications has notably increased. This biopolymer is being widely studied for its interesting properties, such as bioadhesion, antimicrobial activity, biocompatibility, and biodegradability. Other promising properties of CS include its modulation of immunological response, hemostasis, and wound and bone healing activity. In this work, a critical review is performed covering its conventional and novel applications, specially focused on pharmaceutical area, providing a clear picture of the current state of art to serve as a basis to direct future research in this field. Despite all the qualities of this polymer, there are only few CS-based products in the market, so it is a priority to enhance the research to develop new technologies and CS-based systems to enforce this biopolymer in the industry.
{"title":"Chitosan Applications on Pharmaceutical Sciences: A Review","authors":"C. A. B. Nieva, M. Villegas, A. Cid, Analía I Romero, J. Bermudez","doi":"10.2174/2210303109666190404143906","DOIUrl":"https://doi.org/10.2174/2210303109666190404143906","url":null,"abstract":"\u0000\u0000Chitosan (CS) is a biomaterial derived from chitin, known for its excellent biological\u0000properties. One of the most interesting features of CS is its potential for chemical derivatization,\u0000which makes it a versatile material and allows to expand its applications. In the last years, the\u0000interest on this polymer and its pharmaceutical applications has notably increased. This biopolymer is\u0000being widely studied for its interesting properties, such as bioadhesion, antimicrobial activity, biocompatibility,\u0000and biodegradability. Other promising properties of CS include its modulation of immunological\u0000response, hemostasis, and wound and bone healing activity.\u0000\u0000\u0000\u0000In this work, a critical review is performed covering its conventional and novel applications,\u0000specially focused on pharmaceutical area, providing a clear picture of the current state of art to serve as\u0000a basis to direct future research in this field.\u0000\u0000\u0000\u0000Despite all the qualities of this polymer, there are only few CS-based products in the market,\u0000so it is a priority to enhance the research to develop new technologies and CS-based systems to enforce\u0000this biopolymer in the industry.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47321195","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 : 2019-08-20DOI: 10.2174/2210303109666190221155353
V. Sabale, Hardikkumar Chaudhari, P. Sabale
The aim of the present study was to formulate and evaluate floating bioadhesive tablets of Nizatidine which is a competitive, reversible H2-receptor antagonist. Floatingbioadhesive drug delivery system exhibiting a unique combination of floatation and bioadhesion to prolong gastric residence time was prepared. Polymers used were Hydroxy Propyl Methyl Cellulose (HPMC) K15M as matrix forming water swellable release retarding polymer and carbopol 934P as bioadhesive polymer. The gas generating agents used were sodium bicarbonate and citric acid. The prepared floating bioadhesive tablets of Nizatidine were optimized by 32 factorial design to study independent variable X1 (concentration of CP 934P) and X2 (concentration of HPMC K15M) and dependent variables as floating lag time, cumulative percentage drug release at 12h and swelling index. Tablets were evaluated for various parameters such as hardness, friability, drug content, swelling behavior, floating lag time, bioadhesive strength, drug release profile and stability. All the formulations passed the test for weight variation, hardness, content uniformity and showed acceptable results with respect to drug content (97.93 ± 0.57) and % friability. The tablet containing 25% HPMC K15M and 13.75 % Carbopol 934P was selected as optimized formulation which showed the floating lag time of 74.34±2.08 seconds, drug release of 97.03±0.55% at 12 h (R12h,%), S.I as 79.24±0.87 at 9 h and bioadhesive strength as 10.0023±21.47 g. Stability of the formulation was proved using stability study. The formulated tablets have a potential for controlled release of the drug through floatation and bioadhesion.
{"title":"Formulation and In vitro Evaluation of Gastroretentive Floating Bioadhesive Tablets of Nizatidine using Factorial Design","authors":"V. Sabale, Hardikkumar Chaudhari, P. Sabale","doi":"10.2174/2210303109666190221155353","DOIUrl":"https://doi.org/10.2174/2210303109666190221155353","url":null,"abstract":"\u0000\u0000The aim of the present study was to formulate and evaluate floating bioadhesive\u0000tablets of Nizatidine which is a competitive, reversible H2-receptor antagonist. Floatingbioadhesive\u0000drug delivery system exhibiting a unique combination of floatation and bioadhesion to prolong\u0000gastric residence time was prepared.\u0000\u0000\u0000\u0000Polymers used were Hydroxy Propyl Methyl Cellulose (HPMC) K15M as matrix forming\u0000water swellable release retarding polymer and carbopol 934P as bioadhesive polymer. The gas generating\u0000agents used were sodium bicarbonate and citric acid. The prepared floating bioadhesive tablets of\u0000Nizatidine were optimized by 32 factorial design to study independent variable X1 (concentration of CP\u0000934P) and X2 (concentration of HPMC K15M) and dependent variables as floating lag time, cumulative\u0000percentage drug release at 12h and swelling index. Tablets were evaluated for various parameters\u0000such as hardness, friability, drug content, swelling behavior, floating lag time, bioadhesive strength,\u0000drug release profile and stability.\u0000\u0000\u0000\u0000All the formulations passed the test for weight variation, hardness, content uniformity and\u0000showed acceptable results with respect to drug content (97.93 ± 0.57) and % friability. The tablet containing\u000025% HPMC K15M and 13.75 % Carbopol 934P was selected as optimized formulation which\u0000showed the floating lag time of 74.34±2.08 seconds, drug release of 97.03±0.55% at 12 h (R12h,%), S.I\u0000as 79.24±0.87 at 9 h and bioadhesive strength as 10.0023±21.47 g. Stability of the formulation was\u0000proved using stability study.\u0000\u0000\u0000\u0000The formulated tablets have a potential for controlled release of the drug through floatation\u0000and bioadhesion.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42455755","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 : 2019-08-20DOI: 10.2174/2210303109666190411125857
P. Panzade, P. Somani, P. B. Rathi
The top approach to deliver poorly soluble drugs is the use of a highly soluble form. The present study was conducted to enhance the solubility and dissolution of a poorly aqueous soluble drug nevirapine via a pharmaceutical cocrystal. Another objective of the study was to check the potential of the nevirapine cocrystal in the dosage form. A neat and liquid assisted grinding method was employed to prepare nevirapine cocrystals in a 1:1 and 1:2 stoichiometric ratio of drug:coformer by screening various coformers. The prepared cocrystals were preliminary investigated for melting point and saturation solubility. The selected cocrystal was further confirmed by Infrared Spectroscopy (IR), Differential Scanning Calorimetry (DSC), and Xray Powder Diffraction (XRPD). Further, the cocrystal was subjected to in vitro dissolution study and formulation development. The cocrystal of Nevirapine (NVP) with Para-Amino Benzoic Acid (PABA) coformer prepared by neat grinding in 1:2 ratio exhibited greater solubility. The shifts in IR absorption bands, alterations in DSC thermogram, and distinct XRPD pattern showed the formation of the NVP-PABA cocrystal. Dissolution of NVP-PABA cocrystal enhanced by 38% in 0.1N HCl. Immediate release tablets of NVP-PABA cocrystal exhibited better drug release and less disintegration time. A remarkable increase in the solubility and dissolution of NVP was obtained through the cocrystal with PABA. The cocrystal also showed great potential in the dosage form which may provide future direction for other drugs.
{"title":"Nevirapine Pharmaceutical Cocrystal: Design, Development and Formulation","authors":"P. Panzade, P. Somani, P. B. Rathi","doi":"10.2174/2210303109666190411125857","DOIUrl":"https://doi.org/10.2174/2210303109666190411125857","url":null,"abstract":"\u0000\u0000The top approach to deliver poorly soluble drugs is the use of a\u0000highly soluble form. The present study was conducted to enhance the solubility and dissolution of a\u0000poorly aqueous soluble drug nevirapine via a pharmaceutical cocrystal. Another objective of the study\u0000was to check the potential of the nevirapine cocrystal in the dosage form.\u0000\u0000\u0000\u0000A neat and liquid assisted grinding method was employed to prepare nevirapine cocrystals in\u0000a 1:1 and 1:2 stoichiometric ratio of drug:coformer by screening various coformers. The prepared cocrystals\u0000were preliminary investigated for melting point and saturation solubility. The selected cocrystal\u0000was further confirmed by Infrared Spectroscopy (IR), Differential Scanning Calorimetry (DSC), and Xray\u0000Powder Diffraction (XRPD). Further, the cocrystal was subjected to in vitro dissolution study and\u0000formulation development.\u0000\u0000\u0000\u0000The cocrystal of Nevirapine (NVP) with Para-Amino Benzoic Acid (PABA) coformer prepared\u0000by neat grinding in 1:2 ratio exhibited greater solubility. The shifts in IR absorption bands, alterations\u0000in DSC thermogram, and distinct XRPD pattern showed the formation of the NVP-PABA cocrystal.\u0000Dissolution of NVP-PABA cocrystal enhanced by 38% in 0.1N HCl. Immediate release tablets of\u0000NVP-PABA cocrystal exhibited better drug release and less disintegration time.\u0000\u0000\u0000\u0000 A remarkable increase in the solubility and dissolution of NVP was obtained through the\u0000cocrystal with PABA. The cocrystal also showed great potential in the dosage form which may provide\u0000future direction for other drugs.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44237792","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 : 2019-06-18DOI: 10.2174/2210303109666190618102616
Ajay kUMAR Pathania, S. Bhatt, Manish Kumar, V. Saini
The low penetration power and the retention time into the intraocular tissue are the main problems that make difficult for most of the drugs for the ocular drug delivery system. This is for those drugs that are having the low or poor solubility and the low permeability. Nanostructured Lipid Carriers (NLCs) loaded with Itraconazole (ITZ) were formulated with the aim to increase the solubility and enhance the retention time in the intraocular tissue. Methods: The NLCs were prepared by using Pluronic (PF127), stearic acid and oleic acid. Itraconazole loaded Nanostructured lipid carrier were prepared by high-pressure homogenization method and the formulations were prepared and optimized by 3 Level Factorial Design. F6 was selected on the basis of better entrapment efficiency (94.65), optimum particle size (310nm), and percentage cumulative release (68.67%). Scanning electron microscopy revealed spherical Nanostructured lipid carrier in the microemulsion. Nanostructured lipid carrier Irritation test showed the non-irritancy and antifungal activity showed a more inhibition zone as compared to the marketed formulation. Conclusively the optimized Formulation (F6) shows better results for the ocular drug delivery as compared to the marked formulation.
{"title":"Formulation and Optimization of Itraconazole Loaded Novel Nanostructured Lipid Carrier-based Ocular Controlled Release Formulation.","authors":"Ajay kUMAR Pathania, S. Bhatt, Manish Kumar, V. Saini","doi":"10.2174/2210303109666190618102616","DOIUrl":"https://doi.org/10.2174/2210303109666190618102616","url":null,"abstract":"\u0000\u0000The low penetration power and the retention time into the intraocular tissue are the main problems that make difficult for most of the drugs for the ocular drug delivery system. This is for those drugs that are having the low or poor solubility and the low permeability. \u0000\u0000\u0000\u0000Nanostructured Lipid Carriers (NLCs) loaded with Itraconazole (ITZ) were formulated with the aim to increase the solubility and enhance the retention time in the intraocular tissue. Methods: The NLCs were prepared by using Pluronic (PF127), stearic acid and oleic acid. Itraconazole loaded Nanostructured lipid carrier were prepared by high-pressure homogenization method and the formulations were prepared and optimized by 3 Level Factorial Design. \u0000\u0000\u0000\u0000F6 was selected on the basis of better entrapment efficiency (94.65), optimum particle size (310nm), and percentage cumulative release (68.67%). Scanning electron microscopy revealed spherical Nanostructured lipid carrier in the microemulsion. Nanostructured lipid carrier Irritation test showed the non-irritancy and antifungal activity showed a more inhibition zone as compared to the marketed formulation. \u0000\u0000\u0000\u0000Conclusively the optimized Formulation (F6) shows better results for the ocular drug delivery as compared to the marked formulation. \u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45109595","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 : 2019-05-31DOI: 10.2174/2210303109666190214153315
M. Alam, R. Ali, F. Al-Jenoobi, A. Al-Mohizea
The poor solubility of a drug substance is one of the factors which are responsible for poor dissolution and bioavailabity. To enhance the solubility of Ibuprofen using different techniques, and to investigate the effect of carrier matrixes and methods of preparing solid dispersion on physical state and solubility of Ibuprofen. Fusion method, solvent evaporation and effervescence assisted fusion methods were used to prepare solid dispersions of ibuprofen (IBU). Mannitol, polyethylene-glycol-6000, urea, microcrystalline cellulose, calcium carbonate, sugar spheres, sodium chloride, magnesium oxide, titanium dioxide, citric acid, hydroxypropyl-β-cyclodextrin and β-cyclodextrin were used as carrier matrix. Solid dispersions were characterized using scanning electron microscopy and Differential Scanning Calorimetry (DSC). The solubility of IBU powder and its solid dispersions were investigated in water, acidic buffer (pH-1.2) and in phosphate buffer (pH-6.8). In some of the solid dispersions, IBU lost its crystalline structure and converted into amorphous powder. Scanning electron micrographs and DSC thermograms revealed the absence of IBU crystalline particles in few of the solid dispersion matrixes. Solid dispersion comprising amorphous IBU showed remarkable enhancement in its solubility. The IBU-magnesium oxide solid dispersion showed the highest solubility enhancement, followed by IBU-hydroxypropyl-β-cyclodextrin, IBUpolyethylene glycol-6000, IBU-urea and IBU-β-cyclodextrin. The magnesium oxide, hydroxypropyl-β- cyclodextrin and β-cyclodextrin enhanced solubility even at acidic pH. Effervescence assisted fusion technique showed better solubility results than the other two techniques. On the basis of present observations, it can be suggested that the type of carrier matrix, the method of preparation and the pH of the dispersion plays an important role in the solubility of IBU.
{"title":"The Effect of Carrier Matrix and the Method of Preparing Solid Dispersion on Physical State and Solubility of Ibuprofen","authors":"M. Alam, R. Ali, F. Al-Jenoobi, A. Al-Mohizea","doi":"10.2174/2210303109666190214153315","DOIUrl":"https://doi.org/10.2174/2210303109666190214153315","url":null,"abstract":"\u0000\u0000The poor solubility of a drug substance is one of the factors which are responsible\u0000for poor dissolution and bioavailabity.\u0000\u0000\u0000\u0000To enhance the solubility of Ibuprofen using different techniques, and to investigate the effect\u0000of carrier matrixes and methods of preparing solid dispersion on physical state and solubility of\u0000Ibuprofen.\u0000\u0000\u0000\u0000Fusion method, solvent evaporation and effervescence assisted fusion methods were used to\u0000prepare solid dispersions of ibuprofen (IBU). Mannitol, polyethylene-glycol-6000, urea, microcrystalline\u0000cellulose, calcium carbonate, sugar spheres, sodium chloride, magnesium oxide, titanium dioxide,\u0000citric acid, hydroxypropyl-β-cyclodextrin and β-cyclodextrin were used as carrier matrix. Solid dispersions\u0000were characterized using scanning electron microscopy and Differential Scanning Calorimetry\u0000(DSC). The solubility of IBU powder and its solid dispersions were investigated in water, acidic buffer\u0000(pH-1.2) and in phosphate buffer (pH-6.8).\u0000\u0000\u0000\u0000In some of the solid dispersions, IBU lost its crystalline structure and converted into amorphous\u0000powder. Scanning electron micrographs and DSC thermograms revealed the absence of IBU\u0000crystalline particles in few of the solid dispersion matrixes. Solid dispersion comprising amorphous\u0000IBU showed remarkable enhancement in its solubility. The IBU-magnesium oxide solid dispersion\u0000showed the highest solubility enhancement, followed by IBU-hydroxypropyl-β-cyclodextrin, IBUpolyethylene\u0000glycol-6000, IBU-urea and IBU-β-cyclodextrin. The magnesium oxide, hydroxypropyl-β-\u0000cyclodextrin and β-cyclodextrin enhanced solubility even at acidic pH. Effervescence assisted fusion\u0000technique showed better solubility results than the other two techniques.\u0000\u0000\u0000\u0000On the basis of present observations, it can be suggested that the type of carrier matrix,\u0000the method of preparation and the pH of the dispersion plays an important role in the solubility of IBU.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49663071","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 : 2019-05-31DOI: 10.2174/2210303109666190207152927
Marta Casamonti, V. Piazzini, A. Bilia, M. Bergonzi
The skin-PAMPA test is a quick and relatively deep tool in the early stages of drug discovery and formulation of dermal and transdermal delivery systems. This study focused on the application of the skin-PAMPA test to evaluate the permeation of Resveratrol (RSV) and also of two formulations, Liposomes (LP) and Nanostructured Lipid Carriers (NLC), prepared to improve RSV topical delivery. LP and NLC were physically and chemically characterized. Stability and in vitro release studies were also assessed in different pH media. The release results were applied to define the kinetic and mechanism of RSV release from the LP and NLC formulations. In vitro permeability was estimated through the skin-PAMPA and the antioxidant capacity was evaluated by DPPH test. Nanoparticles have a spherical shape, dimensions suitable for skin application, and narrow size distribution. Encapsulation efficiency was 96.5% ± 2.1 for LP and 86.0% ± 2.4 for NLC. The formulations increased RSV solubility. Nanoparticles showed excellent physical and chemical stability during storage at 4°C for two months. In vitro release studies were performed at pH 5.5 and 7.4. The nanoparticles achieved a prolonged release of RSV. Skin-PAMPA proved an increased cutaneous permeability of RSV when loaded into LP or NLC. Both formulations maintained the antioxidant capacity of RSV, as evidenced by DPPH test. LP and NLC could be applied as drug delivery systems suitable for the topical delivery of the RSV. Skin-PAMPA has proved to be an effective tool for studying the permeability not only of the RSV but also of its formulations.
{"title":"Evaluation of Skin Permeability of Resveratrol Loaded Liposomes and Nanostructured Lipid Carriers using a Skin Mimic Artificial Membrane (skin-PAMPA)","authors":"Marta Casamonti, V. Piazzini, A. Bilia, M. Bergonzi","doi":"10.2174/2210303109666190207152927","DOIUrl":"https://doi.org/10.2174/2210303109666190207152927","url":null,"abstract":"\u0000\u0000The skin-PAMPA test is a quick and relatively deep tool in the early stages of\u0000drug discovery and formulation of dermal and transdermal delivery systems.\u0000\u0000\u0000\u0000This study focused on the application of the skin-PAMPA test to evaluate the permeation of\u0000Resveratrol (RSV) and also of two formulations, Liposomes (LP) and Nanostructured Lipid Carriers\u0000(NLC), prepared to improve RSV topical delivery.\u0000\u0000\u0000\u0000LP and NLC were physically and chemically characterized. Stability and in vitro release\u0000studies were also assessed in different pH media. The release results were applied to define the kinetic\u0000and mechanism of RSV release from the LP and NLC formulations. In vitro permeability was estimated\u0000through the skin-PAMPA and the antioxidant capacity was evaluated by DPPH test.\u0000\u0000\u0000\u0000Nanoparticles have a spherical shape, dimensions suitable for skin application, and narrow size\u0000distribution. Encapsulation efficiency was 96.5% ± 2.1 for LP and 86.0% ± 2.4 for NLC. The formulations\u0000increased RSV solubility. Nanoparticles showed excellent physical and chemical stability during\u0000storage at 4°C for two months. In vitro release studies were performed at pH 5.5 and 7.4. The nanoparticles\u0000achieved a prolonged release of RSV. Skin-PAMPA proved an increased cutaneous permeability\u0000of RSV when loaded into LP or NLC. Both formulations maintained the antioxidant capacity of RSV,\u0000as evidenced by DPPH test.\u0000\u0000\u0000\u0000LP and NLC could be applied as drug delivery systems suitable for the topical delivery of\u0000the RSV. Skin-PAMPA has proved to be an effective tool for studying the permeability not only of the\u0000RSV but also of its formulations.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49043642","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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