Pub Date : 2024-10-31DOI: 10.1007/s12247-024-09878-y
Atharva Bhatkande, Sagar Narala, Honghe Wang, Nagarjuna Narala, Indrajeet Karnik, Sateesh Kumar Vemula, Michael A. Repka
Purpose
The current study assessed the potential of a pneumatic 3D printer in developing a taste-masked tablet in a single step. Metronidazole (MTZ) was chosen as the model drug, and Eudragit® E PO was used as a taste-masking polymer to produce taste-masked tablets.
Methods
The study focused on optimizing processing parameters, such as the nozzle's printing speed, the printhead's heating temperature, and the pressure. Oval-shaped tablets were printed with a rectilinear printing pattern of 30% and 100% infill and evaluated for in vitro drug release and taste masking. The 3D-printed tablets are also characterized using Differential Scanning Calorimetry (DSC), Fourier-transform Infrared Spectroscopy (FTIR), and Scanning Electron Microscopy (SEM).
Results
The infill density impacts the drug release profile of the tablets. F9, F10, and F11 displayed desired printability among the formulations, with F9 and F10 exhibiting over 85% drug release within 60 min in the in vitro dissolution study. The F9 formulation, with 30% infill, effectively masked the bitter taste of MTZ in the in vitro dissolution study carried out in a pH 6.8 artificial salivary medium. The observed release was below the tasting threshold concentration of the model drug.
Conclusion
In summary, 3-dimensional extrusion-based printing combines the effects of hot-melt extrusion and fused deposition modeling techniques in a single-step process, demonstrating potential as an alternative to the fused-deposition model 3D printing technique and warranting further exploration.
{"title":"Extrusion-Based Three-Dimensional Printing of Metronidazole Immediate Release Tablets: Impact of Processing Parameters and in Vitro Evaluation","authors":"Atharva Bhatkande, Sagar Narala, Honghe Wang, Nagarjuna Narala, Indrajeet Karnik, Sateesh Kumar Vemula, Michael A. Repka","doi":"10.1007/s12247-024-09878-y","DOIUrl":"10.1007/s12247-024-09878-y","url":null,"abstract":"<div><h3>Purpose</h3><p>The current study assessed the potential of a pneumatic 3D printer in developing a taste-masked tablet in a single step. Metronidazole (MTZ) was chosen as the model drug, and Eudragit® E PO was used as a taste-masking polymer to produce taste-masked tablets.</p><h3>Methods</h3><p>The study focused on optimizing processing parameters, such as the nozzle's printing speed, the printhead's heating temperature, and the pressure. Oval-shaped tablets were printed with a rectilinear printing pattern of 30% and 100% infill and evaluated for in vitro drug release and taste masking. The 3D-printed tablets are also characterized using Differential Scanning Calorimetry (DSC), Fourier-transform Infrared Spectroscopy (FTIR), and Scanning Electron Microscopy (SEM).</p><h3>Results</h3><p>The infill density impacts the drug release profile of the tablets. F9, F10, and F11 displayed desired printability among the formulations, with F9 and F10 exhibiting over 85% drug release within 60 min in the in vitro dissolution study. The F9 formulation, with 30% infill, effectively masked the bitter taste of MTZ in the in vitro dissolution study carried out in a pH 6.8 artificial salivary medium. The observed release was below the tasting threshold concentration of the model drug.</p><h3>Conclusion</h3><p>In summary, 3-dimensional extrusion-based printing combines the effects of hot-melt extrusion and fused deposition modeling techniques in a single-step process, demonstrating potential as an alternative to the fused-deposition model 3D printing technique and warranting further exploration.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"19 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12247-024-09878-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-31DOI: 10.1007/s12247-024-09881-3
Sahar Shafaei Bajestani, Mohammadreza Abbaspour, Abbas Akhgari, Hossein Shahdadi Sardou
<div><h3>Objective</h3><p>The study aimed to identify a film sensitive to microbial decomposition to select an appropriate coating for delivering drugs to the colon.</p><h3>Methods & Materials</h3><p>Different polysaccharides, including xanthan, inulin, carrageenan, and alginate, were made with Eudragit FS 30 D (EFS) by film formation method. The films were screened by performing mechanical tests, swelling percentage, the reduction of dry film mass, the passage of water vapor through (WVT) of the films, and the permeability of the films to the drug in different media similar to the gastrointestinal tract (GIT). Additionally, the films' characteristics were evaluated based on shape (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and differential scanning calorimetry (DSC).</p><h3>Results</h3><p>The film evaluation results revealed that the inulin film had the highest work of failure (WF), % of elongation at break (%E), Tensile strength (TS), and elastic modulus (EM). Also, this film exhibited the highest TS/EM ratio. In contrast, other polysaccharide films exhibited the opposite behavior. The results of the dry film swelling and mass reduction tests in media with 1.2, 6.5, and 6.8 pH, as well as in the SCF medium, showed that in an acidic medium, films containing inulin and alginate have very low swelling and less degraded. In contrast, film containing xanthan showed very high swelling and high dry mass at different pHs. However, the alginate film showed lower swelling and dry mass than the xanthan film at all investigated pHs. The results of evaluating the WVT of the films showed that the highest and lowest WVT related to the films prepared from inulin and alginate, respectively. In addition, the highest ratio of the swelling index in the SCF medium compared to the buffered phosphate medium with pH 6.8 was observed in the film containing inulin. The results of the evaluation of the permeability of the films to the drug in different media similar to the GIT showed that the permeability of the inulin film to the drug in a gastric medium is very low. In contrast, the permeability of this film in the SCF medium significantly increased compared to the buffered medium with pH 6.8. The SEM studies showed that films containing xanthan and carrageenan degraded more than other polysaccharide films at pH 1.2. The evaluation and comparison of films in SCF-containing and non-SCF media showed that the degradation of films in SCF media was more significant. Evaluation of DSC and FTIR showed that the formed film containing EFS polymer lack of interaction with other polysaccharides.</p><h3>Conclusion</h3><p>This study showed that inulin film is a suitable polysaccharide for colonic drug delivery systems due to its suitable mechanical properties, low swelling compared to the liquids of the upper parts of the GIT, and sensitivity to the enzymes in the colon. In other words, film coatings consisting of pH-dependent polymers such as EFS in combination with
{"title":"Screening of Polysaccharide Films Consisting of pH-Dependent Systems in Combination with Microbial Decomposition-Dependent Systems to Determine the Appropriate Coating for Colonic Drug Delivery","authors":"Sahar Shafaei Bajestani, Mohammadreza Abbaspour, Abbas Akhgari, Hossein Shahdadi Sardou","doi":"10.1007/s12247-024-09881-3","DOIUrl":"10.1007/s12247-024-09881-3","url":null,"abstract":"<div><h3>Objective</h3><p>The study aimed to identify a film sensitive to microbial decomposition to select an appropriate coating for delivering drugs to the colon.</p><h3>Methods & Materials</h3><p>Different polysaccharides, including xanthan, inulin, carrageenan, and alginate, were made with Eudragit FS 30 D (EFS) by film formation method. The films were screened by performing mechanical tests, swelling percentage, the reduction of dry film mass, the passage of water vapor through (WVT) of the films, and the permeability of the films to the drug in different media similar to the gastrointestinal tract (GIT). Additionally, the films' characteristics were evaluated based on shape (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and differential scanning calorimetry (DSC).</p><h3>Results</h3><p>The film evaluation results revealed that the inulin film had the highest work of failure (WF), % of elongation at break (%E), Tensile strength (TS), and elastic modulus (EM). Also, this film exhibited the highest TS/EM ratio. In contrast, other polysaccharide films exhibited the opposite behavior. The results of the dry film swelling and mass reduction tests in media with 1.2, 6.5, and 6.8 pH, as well as in the SCF medium, showed that in an acidic medium, films containing inulin and alginate have very low swelling and less degraded. In contrast, film containing xanthan showed very high swelling and high dry mass at different pHs. However, the alginate film showed lower swelling and dry mass than the xanthan film at all investigated pHs. The results of evaluating the WVT of the films showed that the highest and lowest WVT related to the films prepared from inulin and alginate, respectively. In addition, the highest ratio of the swelling index in the SCF medium compared to the buffered phosphate medium with pH 6.8 was observed in the film containing inulin. The results of the evaluation of the permeability of the films to the drug in different media similar to the GIT showed that the permeability of the inulin film to the drug in a gastric medium is very low. In contrast, the permeability of this film in the SCF medium significantly increased compared to the buffered medium with pH 6.8. The SEM studies showed that films containing xanthan and carrageenan degraded more than other polysaccharide films at pH 1.2. The evaluation and comparison of films in SCF-containing and non-SCF media showed that the degradation of films in SCF media was more significant. Evaluation of DSC and FTIR showed that the formed film containing EFS polymer lack of interaction with other polysaccharides.</p><h3>Conclusion</h3><p>This study showed that inulin film is a suitable polysaccharide for colonic drug delivery systems due to its suitable mechanical properties, low swelling compared to the liquids of the upper parts of the GIT, and sensitivity to the enzymes in the colon. In other words, film coatings consisting of pH-dependent polymers such as EFS in combination with","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"19 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-30DOI: 10.1007/s12247-024-09870-6
Zhongfang Zhang, Elaine Xu, Ronald Max Puntil, Nicholas Youwakim, Christina Bagia, Lisa C. Rohan, Sravan Kumar Patel
Purpose
Bacterial Vaginosis (BV), characterized by the overgrowth of pathogenic bacterial species in the female genital tract, is a prevalent vaginal condition among women aged 15–44 years. Metronidazole (MTZ), a nitroimidazole antibiotic, is commonly used to treat BV. However, existing MTZ dosage forms such as gels and suppositories can cause leakage, messiness, potential drug loss, and reduce patient adherence. This study demonstrates the feasibility of 3D printing method for manufacturing MTZ-loaded vaginal films at clinically relevant dose and with varied mucoadhesion.
Methods
Fused deposition modeling (FDM)-based 3D printing was utilized for printing vaginal films from hot-melt extruded MTZ filaments. Two different formulation compositions of MTZ films were investigated to demonstrate the method’s versatility and to produce films with varying performance attributes. Films were characterized for drug content, mechanical and thermal properties, in vitro drug release, mucoadhesion, and cytotoxicity.
Results
Soft and flexible vaginal films loaded with 37.5 mg MTZ were successfully manufactured using 3D printing. The two formulations investigated showed differences in drug release and mucoadhesion. Films were compatible with commensal vaginal Lactobacilli and showed no negative impact on the viability of vaginal epithelial cells.
Conclusion
The study demonstrates the feasibility of utilizing 3D printing as an effective, robust, and viable manufacturing method for producing MTZ vaginal films for BV treatment. These films can offer precise dosing, improved bioretention, and enhanced patient adherence without leakage, positioning them as a promising alternative to existing MTZ dosage forms.
{"title":"Fused Deposition Modeling-Based 3D Printing as a Versatile Technology to Manufacture Vaginal Films Incorporating Metronidazole","authors":"Zhongfang Zhang, Elaine Xu, Ronald Max Puntil, Nicholas Youwakim, Christina Bagia, Lisa C. Rohan, Sravan Kumar Patel","doi":"10.1007/s12247-024-09870-6","DOIUrl":"10.1007/s12247-024-09870-6","url":null,"abstract":"<div><h3>Purpose</h3><p>Bacterial Vaginosis (BV), characterized by the overgrowth of pathogenic bacterial species in the female genital tract, is a prevalent vaginal condition among women aged 15–44 years. Metronidazole (MTZ), a nitroimidazole antibiotic, is commonly used to treat BV. However, existing MTZ dosage forms such as gels and suppositories can cause leakage, messiness, potential drug loss, and reduce patient adherence. This study demonstrates the feasibility of 3D printing method for manufacturing MTZ-loaded vaginal films at clinically relevant dose and with varied mucoadhesion.</p><h3>Methods</h3><p>Fused deposition modeling (FDM)-based 3D printing was utilized for printing vaginal films from hot-melt extruded MTZ filaments. Two different formulation compositions of MTZ films were investigated to demonstrate the method’s versatility and to produce films with varying performance attributes. Films were characterized for drug content, mechanical and thermal properties, in vitro drug release, mucoadhesion, and cytotoxicity.</p><h3>Results</h3><p>Soft and flexible vaginal films loaded with 37.5 mg MTZ were successfully manufactured using 3D printing. The two formulations investigated showed differences in drug release and mucoadhesion. Films were compatible with commensal vaginal Lactobacilli and showed no negative impact on the viability of vaginal epithelial cells.</p><h3>Conclusion</h3><p>The study demonstrates the feasibility of utilizing 3D printing as an effective, robust, and viable manufacturing method for producing MTZ vaginal films for BV treatment. These films can offer precise dosing, improved bioretention, and enhanced patient adherence without leakage, positioning them as a promising alternative to existing MTZ dosage forms.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"19 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142540804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Prednisolone, a synthetic corticosteroid drug, is extensively utilized to treat inflammatory diseases and regulates metabolism and the immune system in cancer treatment. However, these drugs are toxic and cause severe side effects if administrated for long durations and in large doses. This work intends to study the atomistic interactions of popular polymeric carrier like PLGA with the drug and thereby provide insights into achieving better loading and a sustained release.
Methods
Molecular dynamics (MD) simulations of prednisolone (drug) encapsulated in Poly Lactic-co-Glycolic acid (PLGA) are performed in this study. Grand Canonical Monte Carlo (GCMC) simulations with MD simulations are conducted to determine the water penetration in PLGA polymer and polymer stability in water. The investigations from this study encompasses structural and dynamical parameters, including the end-to-end distance, radius of gyration of polymer chains, interaction energy, and diffusion coefficient of the drug.
Results
The polymer-drug interactions are studied and identified from the simulation data of PLGA(75:25) and PLGA(50:50) polymers with prednisolone in an aqueous medium for optimal drug carrying capacity and effective drug release. Also, the polymeric systems of PLGA(75:25) and PLGA(50:50) are analyzed with the water penetrant loading using the Grand Canonical Monte Carlo (GCMC) and MD simulations. Water loading analysis revealed that PLGA(75:25) has the highest swelling compared to PLGA(50:50).
Conclusion
This study highlights the characteristics and critical parameters for developing an optimal drug delivery system by investigating polymer-drug interactions, drug encapsulation, and water uptake in polymers using MD and GCMC simulations.
{"title":"Modelling of Prednisolone Drug Encapsulation in Poly Lactic-co-Glycolic Acid Polymer Carrier Using Molecular Dynamics Simulations","authors":"Sriprasad Acharya, Surabhi Aswath, Srikanth Divi, Bharath Raja Guru, Poulumi Dey, Anoop Kishore Vatti","doi":"10.1007/s12247-024-09880-4","DOIUrl":"10.1007/s12247-024-09880-4","url":null,"abstract":"<div><h3>Purpose</h3><p>Prednisolone, a synthetic corticosteroid drug, is extensively utilized to treat inflammatory diseases and regulates metabolism and the immune system in cancer treatment. However, these drugs are toxic and cause severe side effects if administrated for long durations and in large doses. This work intends to study the atomistic interactions of popular polymeric carrier like PLGA with the drug and thereby provide insights into achieving better loading and a sustained release.</p><h3>Methods</h3><p>Molecular dynamics (MD) simulations of prednisolone (drug) encapsulated in Poly Lactic-co-Glycolic acid (PLGA) are performed in this study. Grand Canonical Monte Carlo (GCMC) simulations with MD simulations are conducted to determine the water penetration in PLGA polymer and polymer stability in water. The investigations from this study encompasses structural and dynamical parameters, including the end-to-end distance, radius of gyration of polymer chains, interaction energy, and diffusion coefficient of the drug.</p><h3>Results</h3><p>The polymer-drug interactions are studied and identified from the simulation data of PLGA(75:25) and PLGA(50:50) polymers with prednisolone in an aqueous medium for optimal drug carrying capacity and effective drug release. Also, the polymeric systems of PLGA(75:25) and PLGA(50:50) are analyzed with the water penetrant loading using the Grand Canonical Monte Carlo (GCMC) and MD simulations. Water loading analysis revealed that PLGA(75:25) has the highest swelling compared to PLGA(50:50).</p><h3>Conclusion</h3><p>This study highlights the characteristics and critical parameters for developing an optimal drug delivery system by investigating polymer-drug interactions, drug encapsulation, and water uptake in polymers using MD and GCMC simulations.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"19 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-24DOI: 10.1007/s12247-024-09876-0
S. Jailani, Prajakta Pathare, Sakshi Kunjir, Kishor Chakraborty, C. K. Dhanapal, Noohu Abdulla Khan, Rajkumar Malayandi
Purpose
Apixaban (APX) is a poorly soluble drug; hence, a micronized active pharmaceutical ingredient (API) is widely used for manufacturing immediate-release (IR) tablets using the dry granulation method (DG). Melt granulation techniques (MGTS) are widely used for enhancing solubility by reducing the crystallinity and/or formation of in situ amorphous forms. The present investigation aims to manufacture APX IR tablets with non-micronized API by MGTS and compare the same with tablets using micronized API manufactured by DG.
Methods
APX 5 mg tablets were manufactured with a nonmicronized API particle size of 195 μm (D90) by MGTS, such as hot melt granulation (HMG) and hot melt extrusion (HME). Slugging/deslugging was selected as a dry granulation method (DG) to manufacture the tablets using a micronized API with a particle size of 25 μm (D90). Drug‒polymer miscibility studies were performed, and polyvinyl alcohol (PVA) was found to be a suitable polymer for MGTS. Both lubricated blends and tablets were characterized using different orthogonal analytical techniques including multi-media dissolution studies.
Results
All the quality attributes for the initial and stable samples were well within the specification limits. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) data of the reference (REF) and DG products showed the crystalline form of the API in the tablets, whereas the HMG and HME tablets showed an amorphous nature. In multimedia dissolution studies, all manufactured batches showed a dissolution efficacy of > 85% in 15 min and, hence dissolution profiles of DG batches were comparable with MGTS.
Conclusion
These findings suggest that MGTS could be adopted for the manufacturing of APX IR tablets using a nonmicronized API. The results show that MGTS is an alternative manufacturing process for DG in the production of APX IR tablets, especially to formulate surfactant-free tablets manufactured with non-micronized API. MGTS provide dissolution similarity with reference product that was due formation of an amorphous form during the manufacturing process. Moreover, MGTS are continuous manufacturing processes, which provide a high degree of manufacturing flexibility.
{"title":"Melt Granulation Techniques as an Alternative Manufacturing Technology for the Generic Development of Apixaban 5 mg Immediate-Release Tablets: A Case Study","authors":"S. Jailani, Prajakta Pathare, Sakshi Kunjir, Kishor Chakraborty, C. K. Dhanapal, Noohu Abdulla Khan, Rajkumar Malayandi","doi":"10.1007/s12247-024-09876-0","DOIUrl":"10.1007/s12247-024-09876-0","url":null,"abstract":"<div><h3>Purpose</h3><p>Apixaban (APX) is a poorly soluble drug; hence, a micronized active pharmaceutical ingredient (API) is widely used for manufacturing immediate-release (IR) tablets using the dry granulation method (DG). Melt granulation techniques (MGTS) are widely used for enhancing solubility by reducing the crystallinity and/or formation of in situ amorphous forms. The present investigation aims to manufacture APX IR tablets with non-micronized API by MGTS and compare the same with tablets using micronized API manufactured by DG.</p><h3>Methods</h3><p>APX 5 mg tablets were manufactured with a nonmicronized API particle size of 195 μm (D<sub>90</sub>) by MGTS, such as hot melt granulation (HMG) and hot melt extrusion (HME). Slugging/deslugging was selected as a dry granulation method (DG) to manufacture the tablets using a micronized API with a particle size of 25 μm (D<sub>90</sub>). Drug‒polymer miscibility studies were performed, and polyvinyl alcohol (PVA) was found to be a suitable polymer for MGTS. Both lubricated blends and tablets were characterized using different orthogonal analytical techniques including multi-media dissolution studies.</p><h3>Results</h3><p>All the quality attributes for the initial and stable samples were well within the specification limits. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) data of the reference (REF) and DG products showed the crystalline form of the API in the tablets, whereas the HMG and HME tablets showed an amorphous nature. In multimedia dissolution studies, all manufactured batches showed a dissolution efficacy of > 85% in 15 min and, hence dissolution profiles of DG batches were comparable with MGTS.</p><h3>Conclusion</h3><p>These findings suggest that MGTS could be adopted for the manufacturing of APX IR tablets using a nonmicronized API. The results show that MGTS is an alternative manufacturing process for DG in the production of APX IR tablets, especially to formulate surfactant-free tablets manufactured with non-micronized API. MGTS provide dissolution similarity with reference product that was due formation of an amorphous form during the manufacturing process. Moreover, MGTS are continuous manufacturing processes, which provide a high degree of manufacturing flexibility.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"19 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-21DOI: 10.1007/s12247-024-09872-4
Vullendula Sai Krishna Anand, Dani Lakshman Yarlagadda, Athira R. Nair, Krishnamurthy Bhat, Swapnil J. Dengale
Purpose
To investigate the physicochemical interactions between concomitantly administered anti-malarial and antiretroviral drugs.
Methods
The physicochemical interactions between antimalarial fixed dose combination i.e., Artemether (A) and Lumefantrine (L) with Nevirapine (N) or Efavirenz (E) were investigated separately. The physical mixtures (ALE and ALN) were subjected to solubility, pH shift dissolution (in phosphate and biorelevant media), solid-state characterisation and ex-vivo permeability studies.
Results
For Artemether-Lumefantrine + Efavirenz (ALE) system, the pH shift dissolution study revealed that artemether concentration in mixture decreased to half of its pure drug dissolution in the presence of Lumefantrine and Efavirenz. Further, solid state characterisation confirms the in-situ conversion of artemether into amorphous form in the presence of Lumefantrine and Efavirenz. Similarly, in the ex-vivo everted gut sac permeability study, permeability of Artemether in the presence of Lumefantrine and Efavirenz decreased by half compared to the permeability of Artemether alone, due to physicochemical interactions. For Artemether-Lumefantrine + Nevirapine (ALN) system, there was no significant change in the dissolution of artemether from the combination and alone. However, the permeability of Artemether was decreased to half of its pure drug permeability in the presence of Lumefantrine and Nevirapine, which may be attributed to the inducation of Cytochrome P450 3A4 and P-glycoprotein enzyme by Nevirapine.
Conclusion
The dissolution and permeability of Artemether in the mixtures were reduced to half of its pure drug dissolution and permeability in the presence of antiretroviral drugs due to physicochemical interactions, which may lead to a decrease in bioavailability. This study’s results reveal concomitant administration of these drugs could lead to treatment failure due to physicochemical interactions.
{"title":"Physicochemical Interactions Between Concomitantly Administered Anti-Retroviral and Anti-Malarial Drug","authors":"Vullendula Sai Krishna Anand, Dani Lakshman Yarlagadda, Athira R. Nair, Krishnamurthy Bhat, Swapnil J. Dengale","doi":"10.1007/s12247-024-09872-4","DOIUrl":"10.1007/s12247-024-09872-4","url":null,"abstract":"<div><h3>Purpose</h3><p>To investigate the physicochemical interactions between concomitantly administered anti-malarial and antiretroviral drugs.</p><h3>Methods</h3><p>The physicochemical interactions between antimalarial fixed dose combination i.e., Artemether (A) and Lumefantrine (L) with Nevirapine (N) or Efavirenz (E) were investigated separately. The physical mixtures (ALE and ALN) were subjected to solubility, pH shift dissolution (in phosphate and biorelevant media), solid-state characterisation and ex-vivo permeability studies.</p><h3>Results</h3><p>For Artemether-Lumefantrine + Efavirenz (ALE) system, the pH shift dissolution study revealed that artemether concentration in mixture decreased to half of its pure drug dissolution in the presence of Lumefantrine and Efavirenz. Further, solid state characterisation confirms the in-situ conversion of artemether into amorphous form in the presence of Lumefantrine and Efavirenz. Similarly, in the ex-vivo everted gut sac permeability study, permeability of Artemether in the presence of Lumefantrine and Efavirenz decreased by half compared to the permeability of Artemether alone, due to physicochemical interactions. For Artemether-Lumefantrine + Nevirapine (ALN) system, there was no significant change in the dissolution of artemether from the combination and alone. However, the permeability of Artemether was decreased to half of its pure drug permeability in the presence of Lumefantrine and Nevirapine, which may be attributed to the inducation of Cytochrome P450 3A4 and P-glycoprotein enzyme by Nevirapine.</p><h3>Conclusion</h3><p>The dissolution and permeability of Artemether in the mixtures were reduced to half of its pure drug dissolution and permeability in the presence of antiretroviral drugs due to physicochemical interactions, which may lead to a decrease in bioavailability. This study’s results reveal concomitant administration of these drugs could lead to treatment failure due to physicochemical interactions.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"19 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amoxicillin's side effects are due to its propensity to disturb gut flora. Prebiotics can aid in reversing the dysbiosis caused by antibiotics by promoting the growth of various indigenous gut flora. The present investigation aims to determine the prebiotic potential of common binders (starch, gelatin, pectin, and guar gum) against L. acidophilus. The further objective is to explore the potential biological advantages of amoxicillin therapy when prepared with potential prebiotic excipients.
Methods
In the current investigation, prebiotic-based amoxicillin granules were prepared by wet granulation method with 81.5 ± 3.26% yield. To ensure their therapeutic outcomes, prepared granules were evaluated based on drug release profile, drug degradation, prebiotic potential, in vitro antimicrobial activity, antioxidant activity, anti-inflammatory activity, and anti-diarrhoeal potential.
Results
After 24, 36, 48 and 60 h of incubation of L. acidophilus in different base materials, it was found that the growth of L. acidophilus was more in pectin, among other binders. Formulated granules showed better intestinal stability and sustained release profile (~ 60% release in 4 h). FTIR, DSC and XRD analyses revealed minimal interaction between the drug and the selected excipients. Granules were found to have superior S. aureus and P. aeruginosa inhibition potential compared with the pure drug and starch formulations. Also, the highest antioxidant activity was observed in the Pectin granules compared to starch granules and the pure drug. IL-6, IL1β, and TNF-α levels of the pectin-treated group show better anti-inflammatory properties than starch formulations and pure drugs. The anti-diarrhoeal effect of pectin was found to be better because it supports the growth of probiotics.
Conclusion
In this study, pectin-based amoxicillin granules were superior in mitigating the gastric distress associated with oral amoxicillin administration. The metabolites of probiotics reduced gut pathogens, inflammation, and oxidation, suggesting that the formulated pectin-amoxicillin granules effectively provide gastroprotection.
{"title":"Gastroprotective Efficacy of Prebiotic-based Oral Formulation of Amoxicillin","authors":"Shashi Supriya, Vineet Kumar Rai, Deepak Pradhan, Jitu Halder, Tushar Kanti Rajwar, Ritu Mahanty, Ivy Saha, Priyanka Dash, Chandan Dash, Saroj Kumar Rout, Jameel Al-Tamimi, Hossan Ebaid, Salim Manoharadas, Biswakanth Kar, Goutam Ghosh, Goutam Rath","doi":"10.1007/s12247-024-09875-1","DOIUrl":"10.1007/s12247-024-09875-1","url":null,"abstract":"<div><h3>Purpose</h3><p>Amoxicillin's side effects are due to its propensity to disturb gut flora. Prebiotics can aid in reversing the dysbiosis caused by antibiotics by promoting the growth of various indigenous gut flora. The present investigation aims to determine the prebiotic potential of common binders (starch, gelatin, pectin, and guar gum) against <i>L. acidophilus</i>. The further objective is to explore the potential biological advantages of amoxicillin therapy when prepared with potential prebiotic excipients.</p><h3>Methods</h3><p>In the current investigation, prebiotic-based amoxicillin granules were prepared by wet granulation method with 81.5 ± 3.26% yield. To ensure their therapeutic outcomes, prepared granules were evaluated based on drug release profile, drug degradation, prebiotic potential, in vitro antimicrobial activity, antioxidant activity, anti-inflammatory activity, and anti-diarrhoeal potential.</p><h3>Results</h3><p>After 24, 36, 48 and 60 h of incubation of <i>L. acidophilus</i> in different base materials, it was found that the growth of <i>L. acidophilus</i> was more in pectin, among other binders. Formulated granules showed better intestinal stability and sustained release profile (~ 60% release in 4 h). FTIR, DSC and XRD analyses revealed minimal interaction between the drug and the selected excipients. Granules were found to have superior <i>S. aureus</i> and <i>P. aeruginosa</i> inhibition potential compared with the pure drug and starch formulations. Also, the highest antioxidant activity was observed in the Pectin granules compared to starch granules and the pure drug. IL-6, IL1β, and TNF-α levels of the pectin-treated group show better anti-inflammatory properties than starch formulations and pure drugs. The anti-diarrhoeal effect of pectin was found to be better because it supports the growth of probiotics.</p><h3>Conclusion</h3><p>In this study, pectin-based amoxicillin granules were superior in mitigating the gastric distress associated with oral amoxicillin administration. The metabolites of probiotics reduced gut pathogens, inflammation, and oxidation, suggesting that the formulated pectin-amoxicillin granules effectively provide gastroprotection.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"19 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-15DOI: 10.1007/s12247-024-09855-5
Vishva Chauhan, Rajnikant Mardia, Mehul Patel, Bhanu Suhagia, Tejal Soni
Purpose
Azelnidipine, a BCS class II antihypertensive medication, is known for its low solubility and high permeability. In order to enhance its properties, generic GRAS (Generally Recognized as Safe) molecules were utilized in combination with crystal engineering to create novel cocrystal forms of azelnidipine.
Methods
By varying the ratios (1:1, 1:2, and 2:1) and utilizing succinic acid and nicotinic acid as building blocks, pharmaceutical cocrystals of azelnidipine were successfully developed. A solvent ultrasonic technique was employed to synthesize these cocrystals, which were then subjected to various analytical techniques such as X-ray diffraction, differential scanning calorimetry, NMR, MASS, and FT-IR to confirm their purity, synthesize cocrystals, and evaluate their stability over a six-month period. X-ray crystal data revealed the characteristics of hydrogen bonding and interactions between the drug and co-formers, while differential scanning calorimetry highlighted differences in thermal behaviour and cocrystal formation.
Results
Upon testing solubility and dissolution rate, it was observed that all cocrystals exhibited faster dissolution and higher equilibrium solubility compared to the parent medication. Among the cocrystals, those formed with succinic acid were found to be the most soluble form of azelnidipine.
Conclusion
Overall, the development of pharmaceutical cocrystals of azelnidipine has shown promising results in enhancing the drug's solubility and dissolution rate, potentially leading to improved therapeutic outcomes.
{"title":"Design and Critical Characterization the Pharmaceutical Cocrystal of Azelnidipine With Coformers for Boosting Physicochemical Properties","authors":"Vishva Chauhan, Rajnikant Mardia, Mehul Patel, Bhanu Suhagia, Tejal Soni","doi":"10.1007/s12247-024-09855-5","DOIUrl":"10.1007/s12247-024-09855-5","url":null,"abstract":"<div><h3>Purpose</h3><p>Azelnidipine, a BCS class II antihypertensive medication, is known for its low solubility and high permeability. In order to enhance its properties, generic GRAS (Generally Recognized as Safe) molecules were utilized in combination with crystal engineering to create novel cocrystal forms of azelnidipine.</p><h3>Methods</h3><p>By varying the ratios (1:1, 1:2, and 2:1) and utilizing succinic acid and nicotinic acid as building blocks, pharmaceutical cocrystals of azelnidipine were successfully developed. A solvent ultrasonic technique was employed to synthesize these cocrystals, which were then subjected to various analytical techniques such as X-ray diffraction, differential scanning calorimetry, NMR, MASS, and FT-IR to confirm their purity, synthesize cocrystals, and evaluate their stability over a six-month period. X-ray crystal data revealed the characteristics of hydrogen bonding and interactions between the drug and co-formers, while differential scanning calorimetry highlighted differences in thermal behaviour and cocrystal formation.</p><h3>Results</h3><p>Upon testing solubility and dissolution rate, it was observed that all cocrystals exhibited faster dissolution and higher equilibrium solubility compared to the parent medication. Among the cocrystals, those formed with succinic acid were found to be the most soluble form of azelnidipine.</p><h3>Conclusion</h3><p>Overall, the development of pharmaceutical cocrystals of azelnidipine has shown promising results in enhancing the drug's solubility and dissolution rate, potentially leading to improved therapeutic outcomes.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"19 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1007/s12247-024-09874-2
Vedashree M. Sharma, T. V. Valsaraj, Heggar Venkataramana Sudeep, Shyamprasad Kodimule, Joby Jacob
Purpose
Caffeine is a naturally occurring central nervous system stimulant, susceptible to absorb faster in the body, and new design strategies are needed to enhance its sustainable release and stability. The development of new vehicles for drug delivery and sustained release is an important field of pharmaceutical research. Hence the goal of this study is to create a Fiber Interlaced Liposome (FIL), as a vehicle for a sustained delivery platform for caffeine using surface modified liposomes by fruit fibers which offers additional protection against degradation.
Method
The powdered FIL-Caffeine was prepared in aqueous phase by addition of the ingredients in sequential order followed by spray-drying. The optimised formulation was analysed for its structural and surface morphological characteristics by using FTIR, SEM, TEM, XRD, Zeta potential, DSC and in vitro release studies also conducted to confirm the formation of true liposomes.
Result
The FIL-Caffeine powder is seen to have a spherical shape, free of any aggregation from the morphological studies by SEM and TEM with fibers intact outside. The Zeta potential (-40.9 mV) reveals the liposomal stability with formation of true liposomes having particle size distribution 150–500 nm. Encapsulation efficiency (74%), thermal stability by DSC, in vitro sustained release study, and stability in simulated gastrointestinal fluids were also done. The sustained release of caffeine was ensured in FIL formulation (43.26%) as compared to the normal caffeine (100%) after 3 h of dialysis for an 8 h study. Furthermore, the FIL-Caffeine demonstrated enhanced stability and release in the simulated gastric fluid (9.84% for FIL-Caffeine in comparison with 5.22% of caffeine) and in the simulated intestinal fluid (9.83% for FIL-Caffeine in comparison with 8.28% of caffeine) proved the stability of the formulation.
Conclusion
The study results suggest that the surface modified liposomal encapsulation by fruit fibers enhanced the sustained release of caffeine and higher stability in stomach acid as well as gastro intestinal fluids which may be favourable for prolonged release applications of the FIL formulations.
{"title":"Sustained Release of Liposomal Caffeine Using Novel Natural Fiber Interlaced Liposomal Technology: Development and Structural Characterisation","authors":"Vedashree M. Sharma, T. V. Valsaraj, Heggar Venkataramana Sudeep, Shyamprasad Kodimule, Joby Jacob","doi":"10.1007/s12247-024-09874-2","DOIUrl":"10.1007/s12247-024-09874-2","url":null,"abstract":"<div><h3>Purpose</h3><p>Caffeine is a naturally occurring central nervous system stimulant, susceptible to absorb faster in the body, and new design strategies are needed to enhance its sustainable release and stability. The development of new vehicles for drug delivery and sustained release is an important field of pharmaceutical research. Hence the goal of this study is to create a Fiber Interlaced Liposome (FIL), as a vehicle for a sustained delivery platform for caffeine using surface modified liposomes by fruit fibers which offers additional protection against degradation.</p><h3>Method</h3><p>The powdered FIL-Caffeine was prepared in aqueous phase by addition of the ingredients in sequential order followed by spray-drying. The optimised formulation was analysed for its structural and surface morphological characteristics by using FTIR, SEM, TEM, XRD, Zeta potential, DSC and in vitro release studies also conducted to confirm the formation of true liposomes.</p><h3>Result</h3><p>The FIL-Caffeine powder is seen to have a spherical shape, free of any aggregation from the morphological studies by SEM and TEM with fibers intact outside. The Zeta potential (-40.9 mV) reveals the liposomal stability with formation of true liposomes having particle size distribution 150–500 nm. Encapsulation efficiency (74%), thermal stability by DSC, in vitro sustained release study, and stability in simulated gastrointestinal fluids were also done. The sustained release of caffeine was ensured in FIL formulation (43.26%) as compared to the normal caffeine (100%) after 3 h of dialysis for an 8 h study. Furthermore, the FIL-Caffeine demonstrated enhanced stability and release in the simulated gastric fluid (9.84% for FIL-Caffeine in comparison with 5.22% of caffeine) and in the simulated intestinal fluid (9.83% for FIL-Caffeine in comparison with 8.28% of caffeine) proved the stability of the formulation.</p><h3>Conclusion</h3><p>The study results suggest that the surface modified liposomal encapsulation by fruit fibers enhanced the sustained release of caffeine and higher stability in stomach acid as well as gastro intestinal fluids which may be favourable for prolonged release applications of the FIL formulations.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"19 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1007/s12247-024-09873-3
Bhaskar Daravath, Sateesh Kumar Vemula, Naveen Chella
Purpose
The present study aimed to improve the dissolution properties of nateglinide, an anionic drug with poor water solubility and a high log P value, which results in decreased solubility in acidic pH environments. Additionally, the research sought to evaluate the effectiveness of the liquisolid compact technique as a simple, scalable, and cost-efficient approach for enhancing the nateglinide dissolution rate.
Methods
Employing the central composite design (CCD), formulations were prepared with microcrystalline cellulose (carrier), colloidal silicon dioxide (coating materials), and polyethylene glycol 400 utilized as a non-volatile vehicle. Utilizing Response Surface Methodology (RSM), the formulation was optimized with drug concentration and excipient ratios as independent variables, while evaluations focused on the angle of repose, Carr’s index, and percentage cumulative drug release as dependent responses.
Results
The findings demonstrated that liquisolid compacts exhibited superior dissolution profiles (99.13%) and favourable flow properties and compressible properties (angle of repose of 20.530 and Carr’s compressibility index of 12.37% compared to directly compressible tablets. Further analyses through FTIR, DSC, and XRD studies indicated that enhanced dissolution of the drug could exist in an amorphous form or molecular dispersion state.
Conclusion
In conclusion, this work successfully established that the liquisolid compact presents a novel method for enhancing the dissolution rate of nateglinide in acidic pH conditions.
目的本研究旨在改善纳格列奈的溶解特性。纳格列奈是一种阴离子药物，水溶性差，对数 P 值高，导致在酸性 pH 环境中溶解度降低。方法采用中心复合设计（CCD），用微晶纤维素（载体）、胶体二氧化硅（涂层材料）和聚乙二醇 400 作为非挥发性载体制备配方。结果研究结果表明，与直接压片相比，液态固体压片表现出优异的溶解曲线（99.13%）、良好的流动性和可压缩性（与直接压片相比，液态固体压片的静止角为 20.530，卡尔压缩指数为 12.37%）。通过傅立叶变换红外光谱（FTIR）、电化学稳定性（DSC）和 X 射线衍射（XRD）研究进行的进一步分析表明，药物溶解度的提高可能以无定形形式或分子分散状态存在。
{"title":"Optimizing Nateglinide Liquisolid Compacts: Achieving Formulation Excellence Through the Quality by Design Approach","authors":"Bhaskar Daravath, Sateesh Kumar Vemula, Naveen Chella","doi":"10.1007/s12247-024-09873-3","DOIUrl":"10.1007/s12247-024-09873-3","url":null,"abstract":"<div><h3>Purpose</h3><p>The present study aimed to improve the dissolution properties of nateglinide, an anionic drug with poor water solubility and a high log P value, which results in decreased solubility in acidic pH environments. Additionally, the research sought to evaluate the effectiveness of the liquisolid compact technique as a simple, scalable, and cost-efficient approach for enhancing the nateglinide dissolution rate.</p><h3>Methods</h3><p>Employing the central composite design (CCD), formulations were prepared with microcrystalline cellulose (carrier), colloidal silicon dioxide (coating materials), and polyethylene glycol 400 utilized as a non-volatile vehicle. Utilizing Response Surface Methodology (RSM), the formulation was optimized with drug concentration and excipient ratios as independent variables, while evaluations focused on the angle of repose, Carr’s index, and percentage cumulative drug release as dependent responses.</p><h3>Results</h3><p>The findings demonstrated that liquisolid compacts exhibited superior dissolution profiles (99.13%) and favourable flow properties and compressible properties (angle of repose of 20.53<sup>0</sup> and Carr’s compressibility index of 12.37% compared to directly compressible tablets. Further analyses through FTIR, DSC, and XRD studies indicated that enhanced dissolution of the drug could exist in an amorphous form or molecular dispersion state.</p><h3>Conclusion</h3><p>In conclusion, this work successfully established that the liquisolid compact presents a novel method for enhancing the dissolution rate of nateglinide in acidic pH conditions.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"19 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142409342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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