Pub Date : 2024-05-07DOI: 10.22159/ijap.2024v16i3.50206
Karrar T. KHUDHAIR ALBO HAMRAH, A. J. NEAMAH Al-SHAIBANI, Inas F. ABDULRAZZAQ
Objective: Lafutidine is a histamine (H2) receptor antagonist utilized for the treatment of gastric ulcer. Its oral bioavailability is low due to poor water solubility and an extensive first-pass hepatic. So, the present work aims to formulate and characterize of an oil in water (o/w) nanoemulsion of lafutidine as oral liquid dosage form and this could enhance drug solubility and improve its bioavailability. Methods: The pseudo-ternary phase diagrams were constructed via titration method. The diagram plots derived from oil, various ratios of surfactant and co-surfactant (S mix), and double distilled water. The selected optimized lafutidine nanoemulsions formula was determined via a variety of investigational studies like particle size, polydispersity index (PDI), zeta potential, pH, drug content and an in vitro drug release. Results: Characterization studies revealed that the optimum formula of nanoemulsions was (NE5), which consist of 0.2% of lafutidine, 30 % of surfactant and co-surfactant (S mix) (3:1), which mean (22.5%of tween 20:7.5% of polyethylene glycol 200 (PEG 200), 10% of peppermint oil and 59.4% of double distilled water. The optimized formula exhibited droplets size (62.56-96.2 nm), PDI (0.11), good pH value (7.1), zeta potential (-32.2 mV), high drug content (99.2%), in vitro release of lafutidine was significantly higher (P<0.05) for NE5. Scanning probe microscopy (SPM) revealed that the droplets size of NE5 was in nano-scale. Conclusion: It is possible to conclude that the optimized formula (NE5) was promised formula of nanoemulsion for increasing the orally delivered lafutidine bioavailability.
{"title":"PREPARATION AND EVALUATION OF LAFUTIDINE NANOEMULSION AS ORAL DELIVERY SYSTEM","authors":"Karrar T. KHUDHAIR ALBO HAMRAH, A. J. NEAMAH Al-SHAIBANI, Inas F. ABDULRAZZAQ","doi":"10.22159/ijap.2024v16i3.50206","DOIUrl":"https://doi.org/10.22159/ijap.2024v16i3.50206","url":null,"abstract":"Objective: Lafutidine is a histamine (H2) receptor antagonist utilized for the treatment of gastric ulcer. Its oral bioavailability is low due to poor water solubility and an extensive first-pass hepatic. So, the present work aims to formulate and characterize of an oil in water (o/w) nanoemulsion of lafutidine as oral liquid dosage form and this could enhance drug solubility and improve its bioavailability.\u0000Methods: The pseudo-ternary phase diagrams were constructed via titration method. The diagram plots derived from oil, various ratios of surfactant and co-surfactant (S mix), and double distilled water. The selected optimized lafutidine nanoemulsions formula was determined via a variety of investigational studies like particle size, polydispersity index (PDI), zeta potential, pH, drug content and an in vitro drug release.\u0000Results: Characterization studies revealed that the optimum formula of nanoemulsions was (NE5), which consist of 0.2% of lafutidine, 30 % of surfactant and co-surfactant (S mix) (3:1), which mean (22.5%of tween 20:7.5% of polyethylene glycol 200 (PEG 200), 10% of peppermint oil and 59.4% of double distilled water. The optimized formula exhibited droplets size (62.56-96.2 nm), PDI (0.11), good pH value (7.1), zeta potential (-32.2 mV), high drug content (99.2%), in vitro release of lafutidine was significantly higher (P<0.05) for NE5. Scanning probe microscopy (SPM) revealed that the droplets size of NE5 was in nano-scale.\u0000Conclusion: It is possible to conclude that the optimized formula (NE5) was promised formula of nanoemulsion for increasing the orally delivered lafutidine bioavailability.","PeriodicalId":13737,"journal":{"name":"International Journal of Applied Pharmaceutics","volume":"118 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141002714","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 : 2024-05-07DOI: 10.22159/ijap.2024v16i3.50260
SPANDANA K., Arun K. Shettar, R. S.
Objective: In this study, plant-based silver nanoparticles were synthesized and characterized from Premna integrifolia leaf extract to test the viability towards anticancer properties. Methods: Preliminary identification of silver nanoparticles was validated by Visual observation and confirmed for the characterization by Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDX) and Fourier-transform Infrared Spectroscopy (FTIR) analysis. Further synthesized nanoparticles were evaluated against non-small lung cancer cells (A549) by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. Results: Aqueous leaf extract of Premna intigrifolia was synthesized for silver nanoparticles and showed an average size from 35nm to 100 nm through SEM studies. EDX showed a strong signal confirming the formation of silver nanoparticles in the metallic silver region at 5Kev, and the FTIR spectrum showed changes in some peaks of the aqueous extract with functional groups. The newly synthesized silver nanoparticles showed significant anticancer properties targeting lung cancer A549 cell line against standard drug Epotoside with a 50% Inhibitory Concentration (IC50) value of 78.431 µg. Conclusion: The results affirm that biosynthesized silver nanoparticles can be used as an alternative to chemical medicines to cure cancer.
{"title":"BIOSYNTHESIS, CHARACTERIZATION AND EVALUATION OF SILVER NANOPARTICLES FROM THE LEAF EXTRACT OF PREMNA INTIGRIFOLIA L. AS A POTENTIAL ANTICANCER AGENT","authors":"SPANDANA K., Arun K. Shettar, R. S.","doi":"10.22159/ijap.2024v16i3.50260","DOIUrl":"https://doi.org/10.22159/ijap.2024v16i3.50260","url":null,"abstract":"Objective: In this study, plant-based silver nanoparticles were synthesized and characterized from Premna integrifolia leaf extract to test the viability towards anticancer properties. \u0000Methods: Preliminary identification of silver nanoparticles was validated by Visual observation and confirmed for the characterization by Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDX) and Fourier-transform Infrared Spectroscopy (FTIR) analysis. Further synthesized nanoparticles were evaluated against non-small lung cancer cells (A549) by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay.\u0000Results: Aqueous leaf extract of Premna intigrifolia was synthesized for silver nanoparticles and showed an average size from 35nm to 100 nm through SEM studies. EDX showed a strong signal confirming the formation of silver nanoparticles in the metallic silver region at 5Kev, and the FTIR spectrum showed changes in some peaks of the aqueous extract with functional groups. The newly synthesized silver nanoparticles showed significant anticancer properties targeting lung cancer A549 cell line against standard drug Epotoside with a 50% Inhibitory Concentration (IC50) value of 78.431 µg.\u0000Conclusion: The results affirm that biosynthesized silver nanoparticles can be used as an alternative to chemical medicines to cure cancer.","PeriodicalId":13737,"journal":{"name":"International Journal of Applied Pharmaceutics","volume":"114 S1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141003511","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 : 2024-05-07DOI: 10.22159/ijap.2024v16i3.50379
Alaa A. Hashim, Dhiya Altememy, Hussein Abdelamir Mohammad, Hasanain Shakir Mahmood, Radhwan M. HUSSEIN, Mahsa Rezaei, Pegah Khosravian
Objective: The main goal was to avoid all the problems associated with usual breast cancer treatment by using 6-thioguanine as a nanostructure lipid carrier (TG-NLCS). This was accomplished by administering an effective and targeted dose of 6-thioguanine (TG) to the tumour site using a long-lasting and biodegradable delivery system. Methods: A combination of heat homogenization and ultrasonication was used to implement the emulsification process. To obtain the optimal formulation, the prepared formulations were first assessed for particle size, Polydispersity Index (PDI), zeta potential, entrapment efficiency, and drug loading capacity. Additionally, a range of physicochemical characterization techniques were employed, including dissolution studies, melting point determination, Fourier-Transform Infrared (FTIR) spectroscopy, and Field Emission Scanning Electron Microscopy (FESEM), as well as cytotoxicity assessment of TG-NLCs in MCF-7 breast cancer cells. Results: The selected formula, TG03, showed a zeta potential of-13.5±0.27 mV and a particle size of 149±0.55 nm. This was further examined using a FESEM. In the in vitro drug release study, the formula demonstrated better-controlled drug release for 48 h in comparison to other formulations. In addition, the significant anti-proliferation activity of TG-NLCs against the MCF-7 breast cancer cell line. Conclusion: Nanostructured lipid carriers (NLCs) are one type of multifunctional nanoparticle that includes many combinations of lipids and medicines for various delivery routes.
{"title":"THE FORMULATION AND EVALUATION OF 6-THIOGUANINE AS A NANOSTRUCTURE LIPID CARRIER FOR THE TARGETED DELIVERY OF BREAST CANCER","authors":"Alaa A. Hashim, Dhiya Altememy, Hussein Abdelamir Mohammad, Hasanain Shakir Mahmood, Radhwan M. HUSSEIN, Mahsa Rezaei, Pegah Khosravian","doi":"10.22159/ijap.2024v16i3.50379","DOIUrl":"https://doi.org/10.22159/ijap.2024v16i3.50379","url":null,"abstract":"Objective: The main goal was to avoid all the problems associated with usual breast cancer treatment by using 6-thioguanine as a nanostructure lipid carrier (TG-NLCS). This was accomplished by administering an effective and targeted dose of 6-thioguanine (TG) to the tumour site using a long-lasting and biodegradable delivery system.\u0000Methods: A combination of heat homogenization and ultrasonication was used to implement the emulsification process. To obtain the optimal formulation, the prepared formulations were first assessed for particle size, Polydispersity Index (PDI), zeta potential, entrapment efficiency, and drug loading capacity. Additionally, a range of physicochemical characterization techniques were employed, including dissolution studies, melting point determination, Fourier-Transform Infrared (FTIR) spectroscopy, and Field Emission Scanning Electron Microscopy (FESEM), as well as cytotoxicity assessment of TG-NLCs in MCF-7 breast cancer cells.\u0000Results: The selected formula, TG03, showed a zeta potential of-13.5±0.27 mV and a particle size of 149±0.55 nm. This was further examined using a FESEM. In the in vitro drug release study, the formula demonstrated better-controlled drug release for 48 h in comparison to other formulations. In addition, the significant anti-proliferation activity of TG-NLCs against the MCF-7 breast cancer cell line.\u0000Conclusion: Nanostructured lipid carriers (NLCs) are one type of multifunctional nanoparticle that includes many combinations of lipids and medicines for various delivery routes.","PeriodicalId":13737,"journal":{"name":"International Journal of Applied Pharmaceutics","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141003828","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 : 2024-05-07DOI: 10.22159/ijap.2024v16i3.50601
Durgaramani Sivadasan
Liposomes have been the delivery of choice for the cancer targeting therapy for the last few decades. Since the 1990s, the development of sterically stabilized (stealth) liposomes has garnered interest for their long circulating half-life. PEGylated (Polyethylene Glycol) liposomes are most extensively studied for delivering cancer therapeutics in a sustained manner. Stealth liposomes are having a less intrinsic toxicity with higher efficacy in cancer treatment. There are numerous clinical trials on the liposomes in tackling cancer is evident for the better outcome of the delivery system. Stealth liposomes are extensively studied for their improved circulation time and better pharmacokinetic profile in cancer treatment. The steric hindrance of the stealth liposomes bypasses the reticuloendothelial system clearance. Further the ligands conjugation in the surface of the liposomes able to achieve better target to the cancer cells. The vascularization nature of the cancerous cells is readily making the liposomal delivery of the cancer drugs accumulate in the cancerous cells rather than healthy cells. There is an utmost need to understand the possible mechanism of stealth liposomes and the basic science behind the development of liposomal delivery system in advancing the cancer treatment with less toxicity. The present review addresses the various modalities of the liposomal development, liposome characterization, mechanism of PEGylated liposomes, the advancements and results of the liposomes in the treatment of various diseases, and the clinical trials and regulatory considerations of liposomal drug delivery system.
{"title":"AN UPDATED REVIEW OF STEALTH LIPOSOMES AND ITS ABILITY TO EVADE THE IMMUNE SYSTEM: A NEW FRONTIER IN CANCER CHEMOTHERAPY","authors":"Durgaramani Sivadasan","doi":"10.22159/ijap.2024v16i3.50601","DOIUrl":"https://doi.org/10.22159/ijap.2024v16i3.50601","url":null,"abstract":"Liposomes have been the delivery of choice for the cancer targeting therapy for the last few decades. Since the 1990s, the development of sterically stabilized (stealth) liposomes has garnered interest for their long circulating half-life. PEGylated (Polyethylene Glycol) liposomes are most extensively studied for delivering cancer therapeutics in a sustained manner. Stealth liposomes are having a less intrinsic toxicity with higher efficacy in cancer treatment. There are numerous clinical trials on the liposomes in tackling cancer is evident for the better outcome of the delivery system. Stealth liposomes are extensively studied for their improved circulation time and better pharmacokinetic profile in cancer treatment. The steric hindrance of the stealth liposomes bypasses the reticuloendothelial system clearance. Further the ligands conjugation in the surface of the liposomes able to achieve better target to the cancer cells. The vascularization nature of the cancerous cells is readily making the liposomal delivery of the cancer drugs accumulate in the cancerous cells rather than healthy cells. There is an utmost need to understand the possible mechanism of stealth liposomes and the basic science behind the development of liposomal delivery system in advancing the cancer treatment with less toxicity. The present review addresses the various modalities of the liposomal development, liposome characterization, mechanism of PEGylated liposomes, the advancements and results of the liposomes in the treatment of various diseases, and the clinical trials and regulatory considerations of liposomal drug delivery system.","PeriodicalId":13737,"journal":{"name":"International Journal of Applied Pharmaceutics","volume":"67 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141003942","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 : 2024-05-07DOI: 10.22159/ijap.2024v16i3.50481
Olga V. Levitskaya, T. Pleteneva, Daria A. Galkina, Nadezhda A. Khodorovich, E. Uspenskaya, Anton V. Syroeshkin
Objective: The aim of this study was to demonstrate that chiral switching should be recognized as a widespread phenomenon that extends beyond the production of pure enantiomeric drugs. Methods: To investigate the optical activity of substances from various chemical classes, enantiomers of chiral compounds (Sigma-Aldrich, USA) were chosen: valine and its racemic form (D-valine, L-valine, and racemic valine with optical purity ≥ 99%), L-ascorbic acid (content ≥ 99%), carbohydrates (D-glucose, D-galactose, L-galactose, contents ≥ 99.5%). Solutions were prepared using deuterium-depleted water (DDW–"light" water, D/H=4 ppm), natural deionized high-ohmic water (BD, D/H=140 ppm), and heavy water (99.9% D2O; Sigma-Aldrich). Optical activity was measured using the Atago POL-1/2 polarimeter. Results: One of the components in the racemic medication mixture can act as an inert agent, exhibit toxicity, or undergo undesirable biotransformation mechanisms, resulting in the formation of products with unknown properties. It has been established that a change in the deuterium/protium (D/H) ratio in water leads to a change in the equilibrium and kinetic characteristics of optically active compounds across various chemical classes, such as amino acids, carboxylic acids, and carbohydrates. An inequality was observed in the absolute values of the optical rotation of the L-and D-isomers of valine and galactose, depending on the D/H isotope ratio. The impact of chiral water clusters on optical rotation accounts for the sudden shift in the specific rotation of dilute solutions (less than 0.5%) of L-ascorbic acid in water, based on the D/H ratio. The influence of the isotopic composition of water was confirmed by studying the temperature-dependent mutarotation kinetics of D-glucose and L-and D-galactose in Arrhenius coordinates. The mutarotation process in natural high-resistivity water is characterized by an activation energy (Ea) of 40.8±1.4 kJ mol-1, while in deuterium-depleted water, Ea = 63.6±3.5 kJ mol-1. This results in a kinetic isotope effect for deuterium (KIED) of 1.6. Conclusion: Methodological approaches have been developed to control chiral switching based on the isotopic composition of water in vivo and in vitro. The study of changes in the optical activity of hierarchical structures in the human body, the influence of solvent properties on the mechanisms of optical rotation, as well as the use of KIED values, can be utilized to monitor various chiral transitions in vitro and living organisms.
{"title":"CHIRAL SWITCHING CONTROL OF PHARMACEUTICAL SUBSTANCES","authors":"Olga V. Levitskaya, T. Pleteneva, Daria A. Galkina, Nadezhda A. Khodorovich, E. Uspenskaya, Anton V. Syroeshkin","doi":"10.22159/ijap.2024v16i3.50481","DOIUrl":"https://doi.org/10.22159/ijap.2024v16i3.50481","url":null,"abstract":"Objective: The aim of this study was to demonstrate that chiral switching should be recognized as a widespread phenomenon that extends beyond the production of pure enantiomeric drugs.\u0000Methods: To investigate the optical activity of substances from various chemical classes, enantiomers of chiral compounds (Sigma-Aldrich, USA) were chosen: valine and its racemic form (D-valine, L-valine, and racemic valine with optical purity ≥ 99%), L-ascorbic acid (content ≥ 99%), carbohydrates (D-glucose, D-galactose, L-galactose, contents ≥ 99.5%). Solutions were prepared using deuterium-depleted water (DDW–\"light\" water, D/H=4 ppm), natural deionized high-ohmic water (BD, D/H=140 ppm), and heavy water (99.9% D2O; Sigma-Aldrich). Optical activity was measured using the Atago POL-1/2 polarimeter.\u0000Results: One of the components in the racemic medication mixture can act as an inert agent, exhibit toxicity, or undergo undesirable biotransformation mechanisms, resulting in the formation of products with unknown properties. It has been established that a change in the deuterium/protium (D/H) ratio in water leads to a change in the equilibrium and kinetic characteristics of optically active compounds across various chemical classes, such as amino acids, carboxylic acids, and carbohydrates. An inequality was observed in the absolute values of the optical rotation of the L-and D-isomers of valine and galactose, depending on the D/H isotope ratio. The impact of chiral water clusters on optical rotation accounts for the sudden shift in the specific rotation of dilute solutions (less than 0.5%) of L-ascorbic acid in water, based on the D/H ratio. The influence of the isotopic composition of water was confirmed by studying the temperature-dependent mutarotation kinetics of D-glucose and L-and D-galactose in Arrhenius coordinates.\u0000The mutarotation process in natural high-resistivity water is characterized by an activation energy (Ea) of 40.8±1.4 kJ mol-1, while in deuterium-depleted water, Ea = 63.6±3.5 kJ mol-1. This results in a kinetic isotope effect for deuterium (KIED) of 1.6.\u0000Conclusion: Methodological approaches have been developed to control chiral switching based on the isotopic composition of water in vivo and in vitro. The study of changes in the optical activity of hierarchical structures in the human body, the influence of solvent properties on the mechanisms of optical rotation, as well as the use of KIED values, can be utilized to monitor various chiral transitions in vitro and living organisms.","PeriodicalId":13737,"journal":{"name":"International Journal of Applied Pharmaceutics","volume":"11 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141004000","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 : 2024-05-07DOI: 10.22159/ijap.2024v16i3.50298
Srilatha Choudhary, Cvs Subrahmanyam, K. Priyanka
Objective: The purpose of the current research was to design a nicorandil formulation with controlled drug release using the principles of osmotic pump technology. Nicorandil is a biopharmaceutical classification system (BCS) class 3 drug, having a shorter plasma elimination half-life and bioavailability of 75 to 80%. Methods: The elementary osmotic pump (EOP) was prepared by coating a cellulose acetate polymer on the prepared core tablet. A 24-factorial design was applied to optimize the parameters for the osmotic tablet. A surface orifice was drilled. Results: Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) results showed that there was no interaction between drugs and excipients. A 24-factorial design was applied to optimize the parameters for the elementary osmotic pump. The optimized batch was characterized for in vitro drug release studies, and the effects of pH, osmotic pressure, and agitation intensity were analyzed. All the batches showed a drug release ranging from 90.48% to 98.78% after 12 hours. There was no change in the drug release pattern at different pHs and agitation intensities. The drug release was found to decrease with the increasing osmotic pressure of the dissolution medium. The results showed that the amounts of sodium chloride and mannitol were positively affecting the drug release, while the plasticizers PEG400 and DBP were not critical. Scanning electron microscopic studies (SEM) showed the integrity and surface morphology of the coating membrane before and after dissolution. The prepared EOP was found to deliver nicorandil at zero-order for up to 12 hours. Conclusion: Nicorandil was developed successfully as a controlled drug delivery during a 12-hour period, with variables optimized by the use of a 24-factorial design.
{"title":"OSMOTIC DRUG DELIVERY SYSTEM OF NICORANDIL: DESIGN AND EVALUATION","authors":"Srilatha Choudhary, Cvs Subrahmanyam, K. Priyanka","doi":"10.22159/ijap.2024v16i3.50298","DOIUrl":"https://doi.org/10.22159/ijap.2024v16i3.50298","url":null,"abstract":"Objective: The purpose of the current research was to design a nicorandil formulation with controlled drug release using the principles of osmotic pump technology. Nicorandil is a biopharmaceutical classification system (BCS) class 3 drug, having a shorter plasma elimination half-life and bioavailability of 75 to 80%.\u0000Methods: The elementary osmotic pump (EOP) was prepared by coating a cellulose acetate polymer on the prepared core tablet. A 24-factorial design was applied to optimize the parameters for the osmotic tablet. A surface orifice was drilled.\u0000Results: Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) results showed that there was no interaction between drugs and excipients. A 24-factorial design was applied to optimize the parameters for the elementary osmotic pump. The optimized batch was characterized for in vitro drug release studies, and the effects of pH, osmotic pressure, and agitation intensity were analyzed. All the batches showed a drug release ranging from 90.48% to 98.78% after 12 hours. There was no change in the drug release pattern at different pHs and agitation intensities. The drug release was found to decrease with the increasing osmotic pressure of the dissolution medium. The results showed that the amounts of sodium chloride and mannitol were positively affecting the drug release, while the plasticizers PEG400 and DBP were not critical. Scanning electron microscopic studies (SEM) showed the integrity and surface morphology of the coating membrane before and after dissolution. The prepared EOP was found to deliver nicorandil at zero-order for up to 12 hours.\u0000Conclusion: Nicorandil was developed successfully as a controlled drug delivery during a 12-hour period, with variables optimized by the use of a 24-factorial design.","PeriodicalId":13737,"journal":{"name":"International Journal of Applied Pharmaceutics","volume":"7 20","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141005058","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 : 2024-05-07DOI: 10.22159/ijap.2024v16i3.49957
Muhammad Ikhsan, Y. Harahap
Breast cancer is the most common cancer around the world and in Indonesia. The most widely used agent for breast cancer treatment is tamoxifen, with a fixed dose of 20 mg per day. Tamoxifen is metabolized by cytochrome P450 3A4 (CYP3A4) and 2D6 (CYP2D6) to endoxifen and 4-hydroxytamoxifen, which have 30-to 100-fold more potent antiestrogenic activity than tamoxifen. High variations of CYP3A4 and CYP2D6 genes can lead to interpatient variability in its metabolites concentration. The dose can be increased to 40 or 60 mg per day based on individual needs. Therapeutic drug monitoring (TDM) is required to measure the concentration of tamoxifen and its metabolites to decide the individualized dose. The measurement of drug levels should use a sensitive, selective, accurate, precise, and reliable bioanalytical method. Various bioanalytical methods have been developed in several matrices: urine, scalp hair, serum, plasma, dried blood spot (DBS), and volumetric absorptive microsampling (VAMS) samples, with different sample preparations, and frequently using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The bioanalytical method of tamoxifen and its metabolites in the DBS sample was more suitable in the TDM application due to the low invasive sampling technique, more stable sample, and rapid sample preparation. Therefore, it is more time-and cost-efficient than the other methods.
{"title":"THE APPLICATION OF BIOANALYTICAL METHOD OF TAMOXIFEN AND ITS ACTIVE METABOLITES FOR THERAPEUTIC DRUG MONITORING IN BREAST CANCER PATIENTS: A REVIEW","authors":"Muhammad Ikhsan, Y. Harahap","doi":"10.22159/ijap.2024v16i3.49957","DOIUrl":"https://doi.org/10.22159/ijap.2024v16i3.49957","url":null,"abstract":"Breast cancer is the most common cancer around the world and in Indonesia. The most widely used agent for breast cancer treatment is tamoxifen, with a fixed dose of 20 mg per day. Tamoxifen is metabolized by cytochrome P450 3A4 (CYP3A4) and 2D6 (CYP2D6) to endoxifen and 4-hydroxytamoxifen, which have 30-to 100-fold more potent antiestrogenic activity than tamoxifen. High variations of CYP3A4 and CYP2D6 genes can lead to interpatient variability in its metabolites concentration. The dose can be increased to 40 or 60 mg per day based on individual needs. Therapeutic drug monitoring (TDM) is required to measure the concentration of tamoxifen and its metabolites to decide the individualized dose. The measurement of drug levels should use a sensitive, selective, accurate, precise, and reliable bioanalytical method. Various bioanalytical methods have been developed in several matrices: urine, scalp hair, serum, plasma, dried blood spot (DBS), and volumetric absorptive microsampling (VAMS) samples, with different sample preparations, and frequently using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The bioanalytical method of tamoxifen and its metabolites in the DBS sample was more suitable in the TDM application due to the low invasive sampling technique, more stable sample, and rapid sample preparation. Therefore, it is more time-and cost-efficient than the other methods.","PeriodicalId":13737,"journal":{"name":"International Journal of Applied Pharmaceutics","volume":"131 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141002139","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}
Objective: To develop and optimise the oral dissolving films of escitalopram oxalate by response surface methodology. Methods: Oral dissolving film compositions were optimized by central composite design. The films are prepared by solvent casting method. Initially, different polymers were screened and based on the results polyvinyl alcohol was selected as polymer, propylene glycol was selected as plasticizer. Concentration of polymer and concentration of plasticizer were fixed as independent variables; tensile strength, percent elongation, elastic modulus and amount dissolved up to 5 min (%D5 min) were taken as responses. Results: The prepared films exhibited good surface characteristics. The thickness, uniformity of weight, surface pH and drug content are within acceptable range. The mechanical properties like tensile strength, folding endurance, percent elongation and elastic modulus were determined. The statistical analysis showed that polymer concentration has a positive effect on disintegration time and the plasticizer concentration has a significant effect on folding endurance. The prepared film relesases nearly 95% at the end of 5 min. The design space was used to optimize the quantities of polymer and plasticizer. The comparison of checkpoint experiment batch responses are corelating with the predicted responses. Conclusion: Escitalopram oxalate oral dissolving films was successfully designed and optimized by response surface method. It was concluded that the prepared films exhibit good mechanical properties and maximum release within 10 min.
{"title":"DESIGN AND OPTIMIZATION OF ESCITALOPRAM OXALATE ORAL DISSOLVING FILMS BY RESPONSE SURFACE METHODOLOGY","authors":"Chennupati Venu Babu, Venkata Ramana MURTHY KOLAPALLI","doi":"10.22159/ijap.2024v16i3.49662","DOIUrl":"https://doi.org/10.22159/ijap.2024v16i3.49662","url":null,"abstract":"Objective: To develop and optimise the oral dissolving films of escitalopram oxalate by response surface methodology.\u0000Methods: Oral dissolving film compositions were optimized by central composite design. The films are prepared by solvent casting method. Initially, different polymers were screened and based on the results polyvinyl alcohol was selected as polymer, propylene glycol was selected as plasticizer. Concentration of polymer and concentration of plasticizer were fixed as independent variables; tensile strength, percent elongation, elastic modulus and amount dissolved up to 5 min (%D5 min) were taken as responses.\u0000Results: The prepared films exhibited good surface characteristics. The thickness, uniformity of weight, surface pH and drug content are within acceptable range. The mechanical properties like tensile strength, folding endurance, percent elongation and elastic modulus were determined. The statistical analysis showed that polymer concentration has a positive effect on disintegration time and the plasticizer concentration has a significant effect on folding endurance. The prepared film relesases nearly 95% at the end of 5 min. The design space was used to optimize the quantities of polymer and plasticizer. The comparison of checkpoint experiment batch responses are corelating with the predicted responses.\u0000Conclusion: Escitalopram oxalate oral dissolving films was successfully designed and optimized by response surface method. It was concluded that the prepared films exhibit good mechanical properties and maximum release within 10 min.","PeriodicalId":13737,"journal":{"name":"International Journal of Applied Pharmaceutics","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141003923","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 : 2024-05-07DOI: 10.22159/ijap.2024v16i3.50434
C. Rajinikanth, K. Kathiresan
Objective: In current research, Self-Nanoemulsifying Super Saturable Drug Delivery Systems S‑SNEDDS was formulated to attain superior drug dissolution and stability. Methods: Using saturated solubility, capryol ® 90, cremophor®-EL, and transcutol HP were used to make S-SNEDDS. Its composition was optimized using the ternary phase diagram. Using the central composite design of Response Surface Methodology, dasatinib-SNEDDS developed responses for droplet size (Y1), polydispersity index (Y2), and % drug released in 15 min (Y3). Various Precipitation Inhibitors were added to optimize SNEDDS (S3) to make S-SNEDDS and evaluate. Results: The optimum formulation was S3, with a particle size of 128 nm and zeta potential of-21 mV. Methylcellulose was shown better supersaturation than other inhibitors. The optimized formulation (F3) was more stable than ordinary SNEDDS due to its more significant zeta potential (-25 mV) and lower particle size (128 nm). Dasatinib was shown to be amorphous in S-SNEDDS using Differential Scanning Calorimetry and X-ray Powder Diffraction. F3 had a higher 90 min release rate (>99%) than pure drug dispersion (26%) and SNEDDS formulation (95%). Conclusion: The results concluded that S-SNEDDS formulation successfully enhanced the dissolution and stability of dasatinib.
{"title":"DEVELOPMENT AND OPTIMIZATION OF SUPER SATURABLE SELF-NANO EMULSIFYING DRUG DELIVERY SYSTEM FOR DASATINIB BY DESIGN OF EXPERIMENT","authors":"C. Rajinikanth, K. Kathiresan","doi":"10.22159/ijap.2024v16i3.50434","DOIUrl":"https://doi.org/10.22159/ijap.2024v16i3.50434","url":null,"abstract":"Objective: In current research, Self-Nanoemulsifying Super Saturable Drug Delivery Systems S‑SNEDDS was formulated to attain superior drug dissolution and stability.\u0000Methods: Using saturated solubility, capryol ® 90, cremophor®-EL, and transcutol HP were used to make S-SNEDDS. Its composition was optimized using the ternary phase diagram. Using the central composite design of Response Surface Methodology, dasatinib-SNEDDS developed responses for droplet size (Y1), polydispersity index (Y2), and % drug released in 15 min (Y3). Various Precipitation Inhibitors were added to optimize SNEDDS (S3) to make S-SNEDDS and evaluate.\u0000Results: The optimum formulation was S3, with a particle size of 128 nm and zeta potential of-21 mV. Methylcellulose was shown better supersaturation than other inhibitors. The optimized formulation (F3) was more stable than ordinary SNEDDS due to its more significant zeta potential (-25 mV) and lower particle size (128 nm). Dasatinib was shown to be amorphous in S-SNEDDS using Differential Scanning Calorimetry and X-ray Powder Diffraction. F3 had a higher 90 min release rate (>99%) than pure drug dispersion (26%) and SNEDDS formulation (95%).\u0000Conclusion: The results concluded that S-SNEDDS formulation successfully enhanced the dissolution and stability of dasatinib.","PeriodicalId":13737,"journal":{"name":"International Journal of Applied Pharmaceutics","volume":"24 15","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141005948","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 : 2024-05-07DOI: 10.22159/ijap.2024v16i3.49242
Yuyun Nailufa, Bambang Widjaja
Objective: Glutathione is one of the antioxidants widely used as an antiaging and skin lightener. Glutathione at a dose of 250 mg/d orally proved useful as an antiaging. At the same time, glutathione topical night cream is effective at a dose of 0.1% for the skin of Indonesian women. Glutathione is one of the antioxidants that has easily oxidized properties in storage. Research purpose to optimize the concentration of kappa carrageenan polymer and surfactan to obtain the optimal physical characteristics of nanosphere system analyzed based on size, PDI, yield, drug loading, entrapment efficiency, dissolution and antioxidant activity. Methods: The most commonly used method of making nanospheres is ionotropic gelation because it has proven effective, easy, and easy to apply. Ionotropic gelation is depend on the tendency of polyelectrolytes to cross connect to develop hydrogel beads often called gelispheres in the existence of counter ions. Nanospheres were prepared by aerosolization ionotropic gelation technique followed by freeze-drying. This method uses carrageenan polymers of 0.5% and 1.0% with the addition of surfactant as a stabilizer. Evaluation parameters are particle size, entrapment efficiency, drug loading, drug release and antioxidant activity. Results: The results of the nanospheres obtained were tested physically and drug activity. Nanospheres successfully formed, with size 382.67±52.24 nm, F2 325.20±4.62 nm, F3 495.39±30.61 nm, and F4 409.80±4.11 nm. The greater the polymer concentration, the greater the value of entrapment efficiency and drug content in the nanosphere. The morphology of the nanosphere is quite good, spherical, with a smooth surface. The release profile shows that glutathione release is quite good but takes a long time, namely F1 73.91±2.17%, F2 75.91±2.76%, F3 78.56±2.82%, and F4 79.56±1.34% in 480 min or 8 h. Antioxidant activity of glutathione-Kappa carrageenan nanospheres with the DPPH method showed that nanospheres have medium or medium category antioxidant activity. Conclusion: The most optimal formula is F4 with 1% kappa-carrageenan concentration and 0.6% KCl.
{"title":"EFFECT OF POLYMER CONCENTRATION AND SURFACTANTS ON PHYSICAL CHARACTERISTICS, DRUG RELEASE AND ANTIOXIDANT ACTIVITY OF GLUTATHIONE-KAPPA CARRAGEENAN NANOSPHERES","authors":"Yuyun Nailufa, Bambang Widjaja","doi":"10.22159/ijap.2024v16i3.49242","DOIUrl":"https://doi.org/10.22159/ijap.2024v16i3.49242","url":null,"abstract":"Objective: Glutathione is one of the antioxidants widely used as an antiaging and skin lightener. Glutathione at a dose of 250 mg/d orally proved useful as an antiaging. At the same time, glutathione topical night cream is effective at a dose of 0.1% for the skin of Indonesian women. Glutathione is one of the antioxidants that has easily oxidized properties in storage. Research purpose to optimize the concentration of kappa carrageenan polymer and surfactan to obtain the optimal physical characteristics of nanosphere system analyzed based on size, PDI, yield, drug loading, entrapment efficiency, dissolution and antioxidant activity.\u0000Methods: The most commonly used method of making nanospheres is ionotropic gelation because it has proven effective, easy, and easy to apply. Ionotropic gelation is depend on the tendency of polyelectrolytes to cross connect to develop hydrogel beads often called gelispheres in the existence of counter ions. Nanospheres were prepared by aerosolization ionotropic gelation technique followed by freeze-drying. This method uses carrageenan polymers of 0.5% and 1.0% with the addition of surfactant as a stabilizer. Evaluation parameters are particle size, entrapment efficiency, drug loading, drug release and antioxidant activity.\u0000Results: The results of the nanospheres obtained were tested physically and drug activity. Nanospheres successfully formed, with size 382.67±52.24 nm, F2 325.20±4.62 nm, F3 495.39±30.61 nm, and F4 409.80±4.11 nm. The greater the polymer concentration, the greater the value of entrapment efficiency and drug content in the nanosphere. The morphology of the nanosphere is quite good, spherical, with a smooth surface. The release profile shows that glutathione release is quite good but takes a long time, namely F1 73.91±2.17%, F2 75.91±2.76%, F3 78.56±2.82%, and F4 79.56±1.34% in 480 min or 8 h. Antioxidant activity of glutathione-Kappa carrageenan nanospheres with the DPPH method showed that nanospheres have medium or medium category antioxidant activity.\u0000Conclusion: The most optimal formula is F4 with 1% kappa-carrageenan concentration and 0.6% KCl.","PeriodicalId":13737,"journal":{"name":"International Journal of Applied Pharmaceutics","volume":"10 S6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141003538","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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