Pub Date : 2024-07-12DOI: 10.1208/s12249-024-02868-w
Hamsa Yaseen Ghadhban, Kawther Khalid Ahmed
Drug solubility and dissolution remain a significant challenge in pharmaceutical formulations. This study aimed to formulate and evaluate repanglinide (RPG) nanosuspension-based buccal fast-dissolving films (BDFs) for dissolution enhancement. RPG nanosuspension was prepared by the antisolvent-precipitation method using multiple hydrophilic polymers, including soluplus®, polyvinyl alcohol, polyvinyl pyrrolidine, poloxamers, and hydroxyl propyl methyl cellulose. The nanosuspension was then directly loaded into BDFs using the solvent casting technique. Twelve formulas were prepared with a particle size range of 81.6-1389 nm and PDI 0.002-1 for the different polymers. Nanosuspensions prepared with soluplus showed a favored mean particle size of 82.6 ± 3.2 nm. The particles were spherical and non-aggregating, as demonstrated by SEM imaging. FTIR showed no interaction between soluplus and RPG. Faster dissolution occurred for the nanosuspension in comparison with pure RPG (complete release vs 60% within 30 min). The nanosuspension was successfully incorporated into BDFs. The optimum film formula showed 28 s disintegration time, and 97.3% RPG released within 10 min. Ex-vivo permeation profiles revealed improved RPG nanosuspension permeation with the cumulative amount of RPG permeated is103.4% ± 10.1 and a flux of 0.00275 mg/cm2/min compared to 39.3% ± 9.57 and a flux of 0.001058 mg/cm2/min for pure RPG. RPG was successfully formulated into nanosuspension that boosted drug dissolution and permeation. The selection of the ultimate NP formula was driven by optimal particle size, distribution, and drug content. Soluplus NPs were shown to be the successful formulations, which were further incorporated into a buccal film. The film was evaluated for ex-vivo permeation, confirming successful RPG formulation with improved performance compared to pure drugs.
{"title":"Nanosuspension-Based Repaglinide Fast-Dissolving Buccal Film for Dissolution Enhancement.","authors":"Hamsa Yaseen Ghadhban, Kawther Khalid Ahmed","doi":"10.1208/s12249-024-02868-w","DOIUrl":"10.1208/s12249-024-02868-w","url":null,"abstract":"<p><p>Drug solubility and dissolution remain a significant challenge in pharmaceutical formulations. This study aimed to formulate and evaluate repanglinide (RPG) nanosuspension-based buccal fast-dissolving films (BDFs) for dissolution enhancement. RPG nanosuspension was prepared by the antisolvent-precipitation method using multiple hydrophilic polymers, including soluplus®, polyvinyl alcohol, polyvinyl pyrrolidine, poloxamers, and hydroxyl propyl methyl cellulose. The nanosuspension was then directly loaded into BDFs using the solvent casting technique. Twelve formulas were prepared with a particle size range of 81.6-1389 nm and PDI 0.002-1 for the different polymers. Nanosuspensions prepared with soluplus showed a favored mean particle size of 82.6 ± 3.2 nm. The particles were spherical and non-aggregating, as demonstrated by SEM imaging. FTIR showed no interaction between soluplus and RPG. Faster dissolution occurred for the nanosuspension in comparison with pure RPG (complete release vs 60% within 30 min). The nanosuspension was successfully incorporated into BDFs. The optimum film formula showed 28 s disintegration time, and 97.3% RPG released within 10 min. Ex-vivo permeation profiles revealed improved RPG nanosuspension permeation with the cumulative amount of RPG permeated is103.4% ± 10.1 and a flux of 0.00275 mg/cm<sup>2</sup>/min compared to 39.3% ± 9.57 and a flux of 0.001058 mg/cm<sup>2</sup>/min for pure RPG. RPG was successfully formulated into nanosuspension that boosted drug dissolution and permeation. The selection of the ultimate NP formula was driven by optimal particle size, distribution, and drug content. Soluplus NPs were shown to be the successful formulations, which were further incorporated into a buccal film. The film was evaluated for ex-vivo permeation, confirming successful RPG formulation with improved performance compared to pure drugs.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589388","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 : 2024-07-11DOI: 10.1208/s12249-024-02882-y
Om Shelke, Krishna Phani Chandra Susarla, Manish Bankar
Vitamin C is extensively used in cosmetic formulation, howbeit stability is the supreme demerit that limits its use in beautifying products. Numerous techniques are being employed to inhibit the degradation of vitamin C caused by formulation components to facilitate the use in skin rejuvenating products. Diverse materials are being exercised in formulation to stabilize the ascorbic acid and ingredients selected in this formulation composition help for stabilization. The initial stable prototype is developed and further optimization is accomplished by applying the design of experiment tools. The stable pharmaceutical formulations were evaluated for the evaluation parameters and designated as two optimized formulations. The analytical method for the assay of ascorbic acid from the United States pharmacopeia and the related substance method from European pharmacopeia has been modified to be used for cream formulation. The DoE design exhibited that the stability of formulation is impacted by citric acid and tartaric acid but not by propylene glycol and glycerin. The analysis results of topical formulations for the evaluation parameter exhibited satisfactory results. The in-vitro release study method has been developed, optimized, and validated to fit the analysis. The in-vitro studies have been performed for selected compositions and both the formulation has similar kinds of release patterns. The stability study as per ICH guidelines exhibited that the product is stable for accelerated, intermediate, and room-temperature storage conditions. The optimized formulation shows constant release and permeation of ascorbic acid through the skin. The formulation with the combinations of citric acid, tartaric acid, and tocopherol is more stable and the degradation of vitamin C has been reduced significantly. The beaucoup strategies in the unique composition help to protect the degradation by inhibiting the multitudinous degradation pathways.
维生素 C 被广泛用于化妆品配方中,但其稳定性是限制其在美容产品中使用的最大缺点。为了抑制配方成分对维生素 C 的降解,以便于在嫩肤产品中使用,人们采用了许多技术。配方中使用了多种材料来稳定抗坏血酸,本配方中选用的成分有助于稳定抗坏血酸。最初的稳定原型已经开发出来,并通过应用实验设计工具完成了进一步优化。对稳定的药物制剂进行了评价参数评估,并将其定为两个优化制剂。对美国药典中测定抗坏血酸的分析方法和欧洲药典中相关物质的方法进行了修改,以用于乳膏制剂。DoE 设计表明,配方的稳定性受柠檬酸和酒石酸的影响,但不受丙二醇和甘油的影响。外用制剂评价参数的分析结果令人满意。体外释放研究方法经过开发、优化和验证,符合分析要求。对选定的组合物进行了体外研究,两种配方都有类似的释放模式。根据 ICH 指南进行的稳定性研究表明,该产品在加速、中间和室温储存条件下都很稳定。优化配方显示出抗坏血酸在皮肤中的持续释放和渗透。含有柠檬酸、酒石酸和生育酚组合的配方更为稳定,维生素 C 的降解显著减少。独特成分中的多种策略有助于通过抑制多种降解途径来保护降解。
{"title":"Understand the Stabilization Engineering of Ascorbic Acid, Mapping the Scheme for Stabilization, and Advancement.","authors":"Om Shelke, Krishna Phani Chandra Susarla, Manish Bankar","doi":"10.1208/s12249-024-02882-y","DOIUrl":"10.1208/s12249-024-02882-y","url":null,"abstract":"<p><p>Vitamin C is extensively used in cosmetic formulation, howbeit stability is the supreme demerit that limits its use in beautifying products. Numerous techniques are being employed to inhibit the degradation of vitamin C caused by formulation components to facilitate the use in skin rejuvenating products. Diverse materials are being exercised in formulation to stabilize the ascorbic acid and ingredients selected in this formulation composition help for stabilization. The initial stable prototype is developed and further optimization is accomplished by applying the design of experiment tools. The stable pharmaceutical formulations were evaluated for the evaluation parameters and designated as two optimized formulations. The analytical method for the assay of ascorbic acid from the United States pharmacopeia and the related substance method from European pharmacopeia has been modified to be used for cream formulation. The DoE design exhibited that the stability of formulation is impacted by citric acid and tartaric acid but not by propylene glycol and glycerin. The analysis results of topical formulations for the evaluation parameter exhibited satisfactory results. The in-vitro release study method has been developed, optimized, and validated to fit the analysis. The in-vitro studies have been performed for selected compositions and both the formulation has similar kinds of release patterns. The stability study as per ICH guidelines exhibited that the product is stable for accelerated, intermediate, and room-temperature storage conditions. The optimized formulation shows constant release and permeation of ascorbic acid through the skin. The formulation with the combinations of citric acid, tartaric acid, and tocopherol is more stable and the degradation of vitamin C has been reduced significantly. The beaucoup strategies in the unique composition help to protect the degradation by inhibiting the multitudinous degradation pathways.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578688","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}
{"title":"Correction: Development of 3D DLP Printed Sustained Release Ibuprofen Tablets and Their Pharmacokinetic Evaluation in Rats.","authors":"Keb Mosley-Kellum, Arvind Bagde, Shawn Spencer, Satyanarayan Dev, Mandip Singh","doi":"10.1208/s12249-024-02877-9","DOIUrl":"10.1208/s12249-024-02877-9","url":null,"abstract":"","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562384","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}
Commercial topical formulations containing itraconazole (poorly water soluble), for mycotic infections, have poor penetration to infection sites beneath the nails and skin thereby necessitating oral administration. To improve penetration, colloidal solutions of itraconazole (G1-G4) containing Poloxamer 188, tween 80, ethanol, and propylene glycol were prepared and incorporated into HFA-134-containing sprays. Formulations were characterized using particle size, drug content, and Fourier-transform infrared spectroscopy (FTIR). In vitro permeation studies were performed using Franz diffusion cells for 8 h. Antimycotic activity on Candida albicans and Trichophyton rubrum was performed using broth micro-dilution and flow cytometry, while cytotoxicity was tested on HaCaT cell lines. Particle size ranged from 39.35-116.80 nm. FTIR and drug content revealed that G1 was the most stable formulation (optimized formulation). In vitro release over 2 h was 45% for G1 and 34% for the cream. There was a twofold increase in skin permeation, fivefold intradermal retention, and a sevenfold increase in nail penetration of G1 over the cream. Minimum fungicidal concentrations (MFC) against C. albicans were 0.156 and 0.313 µg/mL for G1 and cream, respectively. The formulations showed optimum killing kinetics after 48 h. MFC values against T. rubrum were 0.312 and 0.625 µg/mL for the G1 and cream, respectively. Transmission electron microscopy revealed organelle destruction and cell leakage for G1 in both organisms and penetration of keratin layers to destroy T. rubrum. Cytotoxicity evaluation of G1 showed relative safety for skin cells. The G1 formulation showed superior skin permeation, nail penetration, and fungicidal activity compared with the cream formulation.
{"title":"Formulation and Antimycotic Evaluation of Colloidal Itraconazole-Loaded Metered Dose Sprays for Treating Superficial Mycoses.","authors":"Emmanuel Uronnachi, Titpawan Nakpheng, Thaddeus Gugu, Teerapol Srichana","doi":"10.1208/s12249-024-02879-7","DOIUrl":"10.1208/s12249-024-02879-7","url":null,"abstract":"<p><p>Commercial topical formulations containing itraconazole (poorly water soluble), for mycotic infections, have poor penetration to infection sites beneath the nails and skin thereby necessitating oral administration. To improve penetration, colloidal solutions of itraconazole (G1-G4) containing Poloxamer 188, tween 80, ethanol, and propylene glycol were prepared and incorporated into HFA-134-containing sprays. Formulations were characterized using particle size, drug content, and Fourier-transform infrared spectroscopy (FTIR). In vitro permeation studies were performed using Franz diffusion cells for 8 h. Antimycotic activity on Candida albicans and Trichophyton rubrum was performed using broth micro-dilution and flow cytometry, while cytotoxicity was tested on HaCaT cell lines. Particle size ranged from 39.35-116.80 nm. FTIR and drug content revealed that G1 was the most stable formulation (optimized formulation). In vitro release over 2 h was 45% for G1 and 34% for the cream. There was a twofold increase in skin permeation, fivefold intradermal retention, and a sevenfold increase in nail penetration of G1 over the cream. Minimum fungicidal concentrations (MFC) against C. albicans were 0.156 and 0.313 µg/mL for G1 and cream, respectively. The formulations showed optimum killing kinetics after 48 h. MFC values against T. rubrum were 0.312 and 0.625 µg/mL for the G1 and cream, respectively. Transmission electron microscopy revealed organelle destruction and cell leakage for G1 in both organisms and penetration of keratin layers to destroy T. rubrum. Cytotoxicity evaluation of G1 showed relative safety for skin cells. The G1 formulation showed superior skin permeation, nail penetration, and fungicidal activity compared with the cream formulation.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562385","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 : 2024-07-09DOI: 10.1208/s12249-024-02861-3
Aziz Ur Rahman, Munasib Khan, Mir Azam Khan, Maqsood Ur Rehman, Abdullah, Saeed Ahmed
Azithromycin traditional formulations possesses poor oral bioavailability which necessitates development of new formulation with enhanced bioavailability of the drug. The objective of current research was to explore the kinetics and safety profile of the newly developed azithromycin lipid-based nanoformulation (AZM-NF). In the in-vitro study of kinetics profiling, azithromycin (AZM) release was assessed using dialysis membrane enclosing equal quantity of either AZM-NF, oral suspension of azithromycin commercial product (AZM-CP), or azithromycin pure drug (AZM-PD) in simulated intestinal fluid. The ex-vivo study was performed using rabbit intestinal segments in physiological salts solution in a tissue bath. The in-vivo study was investigated by oral administration of AZM to rabbits while taking blood samples at predetermined time-intervals, followed by HPLC analysis. The toxicity study was conducted in rats to observe histopathological changes in rat's internal organs. In the in-vitro study, maximum release was 95.38 ± 4.58% for AZM-NF, 72.79 ± 8.85% for AZM-CP, and 46.13 ± 8.19% for AZM-PD (p < 0.0001). The ex-vivo investigation revealed maximum permeation of 85.68 ± 5.87 for AZM-NF and 64.88 ± 5.87% for AZM-CP (p < 0.001). The in-vivo kinetics showed Cmax 0.738 ± 0.038, and 0.599 ± 0.082 µg/ml with Tmax of 4 and 2 h for AZM-NF and AZM-CP respectively (p < 0.01). Histopathological examination revealed compromised myocardial fibers integrity by AZM-CP only, liver and kidney showed mild aberrations by both formulations, with no remarkable changes in the rest of studied organs. The results showed that AZM-NF exhibited significantly enhanced bioavailability with comparative safer profile to AZM-CP investigated.
{"title":"Pharmacokinetics and Histotoxic Profile of a Novel Azithromycin-Loaded Lipid-Based Nanoformulation.","authors":"Aziz Ur Rahman, Munasib Khan, Mir Azam Khan, Maqsood Ur Rehman, Abdullah, Saeed Ahmed","doi":"10.1208/s12249-024-02861-3","DOIUrl":"10.1208/s12249-024-02861-3","url":null,"abstract":"<p><p>Azithromycin traditional formulations possesses poor oral bioavailability which necessitates development of new formulation with enhanced bioavailability of the drug. The objective of current research was to explore the kinetics and safety profile of the newly developed azithromycin lipid-based nanoformulation (AZM-NF). In the in-vitro study of kinetics profiling, azithromycin (AZM) release was assessed using dialysis membrane enclosing equal quantity of either AZM-NF, oral suspension of azithromycin commercial product (AZM-CP), or azithromycin pure drug (AZM-PD) in simulated intestinal fluid. The ex-vivo study was performed using rabbit intestinal segments in physiological salts solution in a tissue bath. The in-vivo study was investigated by oral administration of AZM to rabbits while taking blood samples at predetermined time-intervals, followed by HPLC analysis. The toxicity study was conducted in rats to observe histopathological changes in rat's internal organs. In the in-vitro study, maximum release was 95.38 ± 4.58% for AZM-NF, 72.79 ± 8.85% for AZM-CP, and 46.13 ± 8.19% for AZM-PD (p < 0.0001). The ex-vivo investigation revealed maximum permeation of 85.68 ± 5.87 for AZM-NF and 64.88 ± 5.87% for AZM-CP (p < 0.001). The in-vivo kinetics showed C<sub>max</sub> 0.738 ± 0.038, and 0.599 ± 0.082 µg/ml with T<sub>max</sub> of 4 and 2 h for AZM-NF and AZM-CP respectively (p < 0.01). Histopathological examination revealed compromised myocardial fibers integrity by AZM-CP only, liver and kidney showed mild aberrations by both formulations, with no remarkable changes in the rest of studied organs. The results showed that AZM-NF exhibited significantly enhanced bioavailability with comparative safer profile to AZM-CP investigated.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562386","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 : 2024-07-03DOI: 10.1208/s12249-024-02867-x
Debanjan Mukherjee, Sarjana Raikwar
Despite ongoing advances in cancer therapy, the results for the treatment of breast cancer are not satisfactory. The advent of nanotechnology promises to be an essential tool to improve drug delivery effectiveness in cancer therapy. Nanotechnology provides an opportunity to enhance the treatment modality by preventing degradation, improving tumour targeting, and controlling drug release. Recent advances have revealed several strategies to prevent cancer metastasis using nano-drug delivery systems (NDDS). These strategies include the design of appropriate nanocarriers loaded with anti-cancer drugs that target the optimization of physicochemical properties, modulate the tumour microenvironment, and target biomimetic techniques. Nanocarriers have emerged as a preferential approach in the chemotropic treatment for breast cancer due to their pivotal role in safeguarding the therapeutic agents against degradation. They facilitate efficient drug concentration in targeted cells, surmount the resistance of drugs, and possess a small size. Nevertheless, these nanocarrier(s) have some limitations, such as less permeability across the barrier and low bioavailability of loaded drugs. To overcome these challenges, integrating external stimuli has been employed, encompassing infrared light, thermal stimulation, microwaves, and X-rays. Among these stimuli, ultrasound-triggered nanocarriers have gained significant attention due to their cost-effectiveness, non-invasive nature, specificity, ability to penetrate tissues, and capacity to deliver elevated drug concentrations to intended targets. This article comprehensively reviews recent advancements in different nanocarriers for breast cancer chemotherapy. It also delves into the associated hurdles and offers valuable insights into the prospective directions for this innovative field.
尽管癌症治疗技术不断进步,但乳腺癌的治疗效果并不令人满意。纳米技术的出现有望成为提高癌症治疗药物输送效果的重要工具。纳米技术通过防止降解、改善肿瘤靶向性和控制药物释放,为加强治疗模式提供了机会。最近的进展揭示了利用纳米给药系统(NDDS)防止癌症转移的几种策略。这些策略包括设计装载抗癌药物的适当纳米载体,以优化理化特性、调节肿瘤微环境和生物仿生技术为目标。纳米载体在保护治疗药物不被降解方面发挥着关键作用,因此已成为乳腺癌化学治疗的首选方法。纳米载体有助于药物在靶细胞中的有效浓度,克服药物的抗药性,而且体积小。然而,这些纳米载体也有一些局限性,如通过屏障的渗透性较差,载入药物的生物利用度较低。为了克服这些挑战,人们采用了整合外部刺激的方法,包括红外光、热刺激、微波和 X 射线。在这些刺激中,超声触发纳米载体因其成本效益、非侵入性、特异性、穿透组织的能力以及向预定靶点输送高浓度药物的能力而备受关注。本文全面回顾了用于乳腺癌化疗的不同纳米载体的最新进展。文章还深入探讨了相关的障碍,并对这一创新领域的未来发展方向提出了宝贵的见解。
{"title":"Recent Update on Nanocarrier(s) as the Targeted Therapy for Breast Cancer.","authors":"Debanjan Mukherjee, Sarjana Raikwar","doi":"10.1208/s12249-024-02867-x","DOIUrl":"10.1208/s12249-024-02867-x","url":null,"abstract":"<p><p>Despite ongoing advances in cancer therapy, the results for the treatment of breast cancer are not satisfactory. The advent of nanotechnology promises to be an essential tool to improve drug delivery effectiveness in cancer therapy. Nanotechnology provides an opportunity to enhance the treatment modality by preventing degradation, improving tumour targeting, and controlling drug release. Recent advances have revealed several strategies to prevent cancer metastasis using nano-drug delivery systems (NDDS). These strategies include the design of appropriate nanocarriers loaded with anti-cancer drugs that target the optimization of physicochemical properties, modulate the tumour microenvironment, and target biomimetic techniques. Nanocarriers have emerged as a preferential approach in the chemotropic treatment for breast cancer due to their pivotal role in safeguarding the therapeutic agents against degradation. They facilitate efficient drug concentration in targeted cells, surmount the resistance of drugs, and possess a small size. Nevertheless, these nanocarrier(s) have some limitations, such as less permeability across the barrier and low bioavailability of loaded drugs. To overcome these challenges, integrating external stimuli has been employed, encompassing infrared light, thermal stimulation, microwaves, and X-rays. Among these stimuli, ultrasound-triggered nanocarriers have gained significant attention due to their cost-effectiveness, non-invasive nature, specificity, ability to penetrate tissues, and capacity to deliver elevated drug concentrations to intended targets. This article comprehensively reviews recent advancements in different nanocarriers for breast cancer chemotherapy. It also delves into the associated hurdles and offers valuable insights into the prospective directions for this innovative field.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496816","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 : 2024-07-03DOI: 10.1208/s12249-024-02876-w
Oluwatoyin A Adeleke, Saba Abedin
Gummy formulations are considered suitable alternatives to traditional oral dosage forms like tablets and capsules due to their merits that include chewability, softness/flexibility, improved drug release, administration without water, appealing organoleptic properties, better patient compliance, easy preparation and usefulness for persons of different ages (e.g. children). Though there is increasing interest in gummy formulations containing drugs, measurable parameters, and specification limits for evaluating their quality are scarce. Quality check forms an essential part of the pharmaceutical development process because drug products must be distributed as consistently stable, safe, and therapeutically effective entities. Consequently, some quality parameters that could contribute to the overall performance of typical gummy formulations were investigated employing six brands of non-medicinal gummies as specimens. Accordingly, key physicochemical and micromechanical characteristics namely adhesiveness (0.009 - 0.028 mJ), adhesive force (0.009 - 0.055 N), chewiness (2.780 - 6.753 N), cohesiveness (0.910 - 0.990), hardness (2.984 - 7.453 N), springiness (0.960 - 1.000), and resilience (0.388 - 0.572), matrix firmness - compression load (2.653 - 6.753 N) and work done (3.288 - 6.829 mJ), rupture (5.315 - 29.016 N), moisture content (< 5%), weight uniformity (< 2.5 g; < 7.5% deviation), and intraoral dissolution pH (≥ 3.5 ≤ 6.8) were quantified to identify measures that may potentially function as specification limits and serve as prospective reference points for evaluating the quality of gummy formulations. Findings from this work contribute to ongoing efforts to standardize the quality control strategies for gummy formulations, particularly those intended for oral drug delivery.
{"title":"Characterization of Prototype Gummy Formulations Provides Insight into Setting Quality Standards.","authors":"Oluwatoyin A Adeleke, Saba Abedin","doi":"10.1208/s12249-024-02876-w","DOIUrl":"10.1208/s12249-024-02876-w","url":null,"abstract":"<p><p>Gummy formulations are considered suitable alternatives to traditional oral dosage forms like tablets and capsules due to their merits that include chewability, softness/flexibility, improved drug release, administration without water, appealing organoleptic properties, better patient compliance, easy preparation and usefulness for persons of different ages (e.g. children). Though there is increasing interest in gummy formulations containing drugs, measurable parameters, and specification limits for evaluating their quality are scarce. Quality check forms an essential part of the pharmaceutical development process because drug products must be distributed as consistently stable, safe, and therapeutically effective entities. Consequently, some quality parameters that could contribute to the overall performance of typical gummy formulations were investigated employing six brands of non-medicinal gummies as specimens. Accordingly, key physicochemical and micromechanical characteristics namely adhesiveness (0.009 - 0.028 mJ), adhesive force (0.009 - 0.055 N), chewiness (2.780 - 6.753 N), cohesiveness (0.910 - 0.990), hardness (2.984 - 7.453 N), springiness (0.960 - 1.000), and resilience (0.388 - 0.572), matrix firmness - compression load (2.653 - 6.753 N) and work done (3.288 - 6.829 mJ), rupture (5.315 - 29.016 N), moisture content (< 5%), weight uniformity (< 2.5 g; < 7.5% deviation), and intraoral dissolution pH (≥ 3.5 ≤ 6.8) were quantified to identify measures that may potentially function as specification limits and serve as prospective reference points for evaluating the quality of gummy formulations. Findings from this work contribute to ongoing efforts to standardize the quality control strategies for gummy formulations, particularly those intended for oral drug delivery.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496814","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}
Berberine is used in the treatment of metabolic syndrome and its low solubility and very poor oral bioavailability of berberine was one of the primary hurdles for its market approval. This study aimed to improve the solubility and bioavailability of berberine by preparing pellet formulations containing drug-excipient complex (obtained by solid dispersion). Berberine-excipient solid dispersion complexes were obtained with different ratios by the solvent evaporation method. The maximum saturation solubility test was performed as a key factor for choosing the optimal complex for the drug-excipient. The properties of these complexes were investigated by FTIR, DSC, XRD and dissolution tests. The obtained pellets were evaluated and compared in terms of pelletization efficiency, particle size, mechanical strength, sphericity and drug release profile in simulated media of gastric and intestine. Solid-state analysis showed complex formation between the drug and excipients used in solid dispersion. The optimal berberine-phospholipid complex showed a 2-fold increase and the optimal berberine-gelucire and berberine-citric acid complexes showed more than a 3-fold increase in the solubility of berberine compared to pure berberine powder. The evaluation of pellets from each of the optimal complexes showed that the rate and amount of drug released from all pellet formulations in the simulated gastric medium were significantly lower than in the intestine medium. The results of this study showed that the use of berberine-citric acid or berberine-gelucire complex could be considered a promising technique to increase the saturation solubility and improve the release characteristics of berberine from the pellet formulation.
{"title":"Preparation and Evaluation of Berberine-Excipient Complexes in Enhancing the Dissolution Rate of Berberine Incorporated into Pellet Formulations.","authors":"Mohammadreza Abbaspour, Faezeh Faeznia, Parisa Zanjanian, Milad Ruzbehi, Kamran Shourgashti, Amirhosseinn Ziaee, Hossein Shahdadi Sardou, Ali Nokhodchi","doi":"10.1208/s12249-024-02863-1","DOIUrl":"10.1208/s12249-024-02863-1","url":null,"abstract":"<p><p>Berberine is used in the treatment of metabolic syndrome and its low solubility and very poor oral bioavailability of berberine was one of the primary hurdles for its market approval. This study aimed to improve the solubility and bioavailability of berberine by preparing pellet formulations containing drug-excipient complex (obtained by solid dispersion). Berberine-excipient solid dispersion complexes were obtained with different ratios by the solvent evaporation method. The maximum saturation solubility test was performed as a key factor for choosing the optimal complex for the drug-excipient. The properties of these complexes were investigated by FTIR, DSC, XRD and dissolution tests. The obtained pellets were evaluated and compared in terms of pelletization efficiency, particle size, mechanical strength, sphericity and drug release profile in simulated media of gastric and intestine. Solid-state analysis showed complex formation between the drug and excipients used in solid dispersion. The optimal berberine-phospholipid complex showed a 2-fold increase and the optimal berberine-gelucire and berberine-citric acid complexes showed more than a 3-fold increase in the solubility of berberine compared to pure berberine powder. The evaluation of pellets from each of the optimal complexes showed that the rate and amount of drug released from all pellet formulations in the simulated gastric medium were significantly lower than in the intestine medium. The results of this study showed that the use of berberine-citric acid or berberine-gelucire complex could be considered a promising technique to increase the saturation solubility and improve the release characteristics of berberine from the pellet formulation.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496815","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 : 2024-07-01DOI: 10.1208/s12249-024-02873-z
Mercy A Okezue, Chidi Uche, Adekoya Adebola, Stephen R Byrn
Bedaquiline (BQ) solid lipid nanoparticles (SLNs), which have previously been formulated for parenteral administration, have a risk of patient non-compliance in treating tuberculosis. This research presents a strategy to develop BQ SLNs for oral delivery to improve patient adherence, The upper and lower levels for the formulation excipients were generated from screening experiments. Using 4 input factors (BQ, lecithin, Tween 80, and PEG), a full factorial design from 3 × 2x2 × 2 experiments was randomly arranged to investigate 3 response variables: Particle size distribution (PSD), polydispersity index (PdI), and zeta potential (ZP). High shear homogenization was used to mix the solvent and aqueous phases, with 15% sucrose as a cryoprotectant. The response variables were assessed using a zeta sizer while TEM micrographs confirmed the PSD data. Solid-state assessments were conducted using powdered X-ray diffraction and scanning electron microscopy (SEM) imaging. A comparative invitro assessment was used to determine drug release from an equivalent dose of BQ free base powder and BQ-SLN, both packed in hard gelatin capsules. The sonicated formulations obtained significant effects for PSD, PdI, and ZP. The p-values (0.0001 for PdI, 0.0091 for PSD) for BQ as an independent variable in the sonicated formulation were notably higher than those in the unsonicated formulation (0.1336 for PdI, 0.0117 for PSD). The SEM images were between 100 - 400 nm and delineated nanocrystals of BQ embedded in the lipid matrix. The SLN formulation provides higher drug levels over the drug's free base; a similarity factor (f2 = 18.3) was estimated from the dissolution profiles.
{"title":"A Quality by Design Approach for Optimizing Solid Lipid Nanoparticles of Bedaquiline for Improved Product Performance.","authors":"Mercy A Okezue, Chidi Uche, Adekoya Adebola, Stephen R Byrn","doi":"10.1208/s12249-024-02873-z","DOIUrl":"10.1208/s12249-024-02873-z","url":null,"abstract":"<p><p>Bedaquiline (BQ) solid lipid nanoparticles (SLNs), which have previously been formulated for parenteral administration, have a risk of patient non-compliance in treating tuberculosis. This research presents a strategy to develop BQ SLNs for oral delivery to improve patient adherence, The upper and lower levels for the formulation excipients were generated from screening experiments. Using 4 input factors (BQ, lecithin, Tween 80, and PEG), a full factorial design from 3 × 2x2 × 2 experiments was randomly arranged to investigate 3 response variables: Particle size distribution (PSD), polydispersity index (PdI), and zeta potential (ZP). High shear homogenization was used to mix the solvent and aqueous phases, with 15% sucrose as a cryoprotectant. The response variables were assessed using a zeta sizer while TEM micrographs confirmed the PSD data. Solid-state assessments were conducted using powdered X-ray diffraction and scanning electron microscopy (SEM) imaging. A comparative invitro assessment was used to determine drug release from an equivalent dose of BQ free base powder and BQ-SLN, both packed in hard gelatin capsules. The sonicated formulations obtained significant effects for PSD, PdI, and ZP. The p-values (0.0001 for PdI, 0.0091 for PSD) for BQ as an independent variable in the sonicated formulation were notably higher than those in the unsonicated formulation (0.1336 for PdI, 0.0117 for PSD). The SEM images were between 100 - 400 nm and delineated nanocrystals of BQ embedded in the lipid matrix. The SLN formulation provides higher drug levels over the drug's free base; a similarity factor (f2 = 18.3) was estimated from the dissolution profiles.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490464","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}
Silibinin (SIL) Encapsulated Nanoliquid Crystalline (SIL-NLCs) particles were prepared to study neuroprotective effect against amyloid beta (Aβ1-42) neurotoxicity in Balb/c mice model. Theses NLCs were prepared through hot emulsification and probe sonication technique. The pharmacodynamics was investigatigated on Aβ1-42 intracerebroventricular (ICV) injected Balb/c mice. The particle size, zeta potential and drug loading were optimized to be 153 ± 2.5 nm, -21 mV, and 8.2%, respectively. Small angle X-ray (SAXS) and electron microscopy revealed to crystalline shape of SIL-NLCs. Thioflavin T (ThT) fluroscence and circular dichroism (CD) technique were employed to understand monomer inhibition effect of SIL-NLCs on Aβ1-4. In neurobehavioral studies, SIL-NLCs exhibited enhanced mitigation of memory impairment induced on by Aβ1-42 in T-maze and new object recognition test (NORT). Whereas biochemical and histopathological estimation of brain samples showed reduction in level of Aβ1-42 aggregate, acetylcholine esterase (ACHE) and reactive oxygen species (ROS). SIL-NLCs treated animal group showed higher protection against Aβ1-42 toxicity compared to free SIL and Donopezil (DPZ). Therefore SIL-NLCs promises great prospect in neurodegenerative diseases such as Alzheimer's disease.
{"title":"Formulation and Characterization of Silibinin Entrapped Nano-Liquid Crystals for Activity against Aβ<sub>1-42</sub> Neurotoxicity in In-Vivo Model.","authors":"Ajit Singh, Debarati Rakshit, Ankit Kumar, Awanish Mishra, Rahul Shukla","doi":"10.1208/s12249-024-02859-x","DOIUrl":"10.1208/s12249-024-02859-x","url":null,"abstract":"<p><p>Silibinin (SIL) Encapsulated Nanoliquid Crystalline (SIL-NLCs) particles were prepared to study neuroprotective effect against amyloid beta (Aβ<sub>1-42</sub>) neurotoxicity in Balb/c mice model. Theses NLCs were prepared through hot emulsification and probe sonication technique. The pharmacodynamics was investigatigated on Aβ<sub>1-42</sub> intracerebroventricular (ICV) injected Balb/c mice. The particle size, zeta potential and drug loading were optimized to be 153 ± 2.5 nm, -21 mV, and 8.2%, respectively. Small angle X-ray (SAXS) and electron microscopy revealed to crystalline shape of SIL-NLCs. Thioflavin T (ThT) fluroscence and circular dichroism (CD) technique were employed to understand monomer inhibition effect of SIL-NLCs on Aβ<sub>1-4</sub>. In neurobehavioral studies, SIL-NLCs exhibited enhanced mitigation of memory impairment induced on by Aβ<sub>1-42</sub> in T-maze and new object recognition test (NORT). Whereas biochemical and histopathological estimation of brain samples showed reduction in level of Aβ<sub>1-42</sub> aggregate<sub>,</sub> acetylcholine esterase (ACHE) and reactive oxygen species (ROS). SIL-NLCs treated animal group showed higher protection against Aβ<sub>1-42</sub> toxicity compared to free SIL and Donopezil (DPZ). Therefore SIL-NLCs promises great prospect in neurodegenerative diseases such as Alzheimer's disease.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490474","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}