Formulation of Lipid-Based Tableted Spray-Congealed Microparticles for Sustained Release of Vildagliptin: In Vitro and In Vivo Studies

Spray-congealing (SPC) technology was utilized to prepare lipid-based microparticles (MP) capable of sustaining the release of Vildagliptin (VG) for use as a once-daily treatment for type 2 diabetes mellitus. VG microparticles were prepared using Compritol® and Gelucire®50/13 as lipid carriers in the presence of various amounts of Carbomer 934 NF. The lipid carriers were heated to 10 °C above their melting points, and VG was dispersed in the lipid melt and sprayed through the heated two-fluid nozzle of the spray congealer to prepare the VG-loaded MP (VGMP). The microparticles produced were then compressed into tablets and characterized for their morphological and physicochemical characteristics, content analysis, in vitro dissolution, and in vivo bioavailability studies in mixed-breed dogs. The VGMP were spherical with a yield of 76% of the total amount. VG was found to be in its semicrystalline form, with a drug content of 11.11% per tablet and a percentage drug recovery reaching 98.8%. The in vitro dissolution studies showed that VG was released from the tableted particles in a sustained-release fashion for up to 24 h compared with the immediate-release marketed tablets from which VG was completely released within 30 min. The in vivo pharmacokinetics studies reported a Cmax, Tmax, T1/2, and MRT of 118 ng/mL, 3.4 h, 5.27 h, and 9.8 h, respectively, for the SPC formulations, showing a significant difference (p < 0.05)) from the pk parameters of the immediate-release marketed drug (147 ng/mL, 1 h, 2.16 h, and 2.8 h, respectively). The area under the peak (AUC) of both the reference and tested formulations was comparable to indicate similar bioavailabilities. The in vitro–in vivo correlation (IVIVC) studies using multiple level C correlations showed a linear correlation between in vivo pharmacokinetics and dissolution parameters. In conclusion, SPC was successfully utilized to prepare a once-daily sustained-release VG oral drug delivery system.

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PLGA-PEG-PLGA triblock copolymeric micelles as oral drug delivery system: In vitro drug release and in vivo pharmacokinetics assessment

Journal of Colloid and Interface Science ◽

10.1016/j.jcis.2016.11.089 ◽

2017 ◽

Vol 490 ◽

pp. 542-552 ◽

Cited By ~ 44

Author(s):

Xiufen Chen ◽

Jianzhong Chen ◽

Bowen Li ◽

Xiang Yang ◽

Rongjie Zeng ◽

...

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Drug Delivery System ◽

Oral Drug Delivery ◽

Oral Drug ◽

In Vitro Drug Release ◽

Oral Drug Delivery System ◽

In Vivo Pharmacokinetics

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Development and In Vitro-In Vivo Evaluation of a Novel Sustained-Release Loxoprofen Pellet with Double Coating Layer

Pharmaceutics ◽

10.3390/pharmaceutics11060260 ◽

2019 ◽

Vol 11 (6) ◽

pp. 260 ◽

Cited By ~ 4

Author(s):

Dongwei Wan ◽

Min Zhao ◽

Jingjing Zhang ◽

Libiao Luan

Keyword(s):

Citric Acid ◽

Drug Release ◽

Sustained Release ◽

Release Rate ◽

Diffusion Rate ◽

Immediate Release ◽

Pharmacokinetic Studies ◽

Release Tablet

This study aimed to develop a novel sustained release pellet of loxoprofen sodium (LXP) by coating a dissolution-rate controlling sub-layer containing hydroxypropyl methyl cellulose (HPMC) and citric acid, and a second diffusion-rate controlling layer containing aqueous dispersion of ethyl cellulose (ADEC) on the surface of a LXP conventional pellet, and to compare its performance in vivo with an immediate release tablet (Loxinon®). A three-level, three-factor Box-Behnken design and the response surface model (RSM) were used to investigate and optimize the effects of the citric acid content in the sub-layer, the sub-layer coating level, and the outer ADEC coating level on the in vitro release profiles of LXP sustained release pellets. The pharmacokinetic studies of the optimal sustained release pellets were performed in fasted beagle dogs using an immediate release tablet as a reference. The results illustrated that both the citric acid (CA) and ADEC as the dissolution- and diffusion-rate controlling materials significantly decreased the drug release rate. The optimal formulation showed a pH-independent drug release in media at pH above 4.5 and a slightly slow release in acid medium. The pharmacokinetic studies revealed that a more stable and prolonged plasma drug concentration profile of the optimal pellets was achieved, with a relative bioavaibility of 87.16% compared with the conventional tablets. This article provided a novel concept of two-step control of the release rate of LXP, which showed a sustained release both in vitro and in vivo.

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Bilayer tablets with sustained-release metformin and immediate-release sitagliptin: preparation and in vitro/in vivo evaluation

Journal of Pharmaceutical Investigation ◽

10.1007/s40005-021-00533-z ◽

2021 ◽

Author(s):

Ngoc Nha Thao Nguyen ◽

Duy Toan Pham ◽

Duc Tuan Nguyen ◽

Thi Thu Loan Trinh

Keyword(s):

Sustained Release ◽

Immediate Release ◽

In Vivo Evaluation ◽

Bilayer Tablets

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In vitro dissolution method fitted to in vivo absorption profile of rivaroxaban immediate-release tablets applying in silico data

Drug Development and Industrial Pharmacy ◽

10.1080/03639045.2017.1411939 ◽

2017 ◽

Vol 44 (5) ◽

pp. 723-728 ◽

Cited By ~ 1

Author(s):

Nathalie R. Wingert ◽

Natália O. dos Santos ◽

Sarah C. Campanharo ◽

Elisa S. Simon ◽

Nadia M. Volpato ◽

...

Keyword(s):

In Silico ◽

Immediate Release ◽

In Vitro Dissolution ◽

Absorption Profile ◽

Dissolution Method ◽

In Vivo Absorption

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Requirements for Additional Strength Biowaivers for Modified Release Solid Oral Dosage Forms in International Pharmaceutical Regulators Programme Participating Regulators and Organisations: Differences and Commonalities

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/jpps32260 ◽

2021 ◽

Vol 24 ◽

pp. 548-562

Author(s):

Matthias Shona Roost ◽

Henrike Potthast ◽

Chantal Walther ◽

Alfredo García-Arieta ◽

Ivana Abalos ◽

...

Keyword(s):

Immediate Release ◽

Dosage Forms ◽

Oral Dosage ◽

In Vitro Dissolution ◽

Quantitative Composition ◽

Modified Release ◽

Solid Oral Dosage Forms ◽

Oral Dosage Forms

This article describes an overview of waivers of in vivo bioequivalence studies for additional strengths in the context of the registration of modified release generic products and is a follow-up to the recent publication for the immediate release solid oral dosage forms. The current paper is based on a survey among the participating members of the Bioequivalence Working Group for Generics (BEWGG) of the International Pharmaceutical Regulators Program (IPRP) regarding this topic. Most jurisdictions consider the extrapolation of bioequivalence results obtained with one (most sensitive) strength of a product series as less straightforward for modified release products than for immediate release products. There is consensus that modified release products should demonstrate bioequivalence not only in the fasted state but also in the fed state, but differences exist regarding the necessity of additional multiple dose studies. Fundamental differences between jurisdictions are revealed regarding requirements on the quantitative composition of different strengths and the differentiation of single and multiple unit dosage forms. Differences in terms of in vitro dissolution requirements are obvious, though these are mostly related to possible additional comparative investigations rather than regarding the need for product-specific methods. As with the requirements for immediate release products, harmonization of the various regulations for modified release products is highly desirable to conduct the appropriate studies from a scientific point of view, thus ensuring therapeutic equivalence.

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Formulation and characterization of a paediatric nanoemulsion dosage form with modified oral drug delivery system for improved dissolution rate of nevirapine

MRS Advances ◽

10.1557/adv.2018.320 ◽

2018 ◽

Vol 3 (37) ◽

pp. 2203-2219 ◽

Cited By ~ 3

Author(s):

Tapiwa E. Manyarara ◽

Star Khoza ◽

Admire Dube ◽

Chiedza C. Maponga

Keyword(s):

Drug Release ◽

Dissolution Rate ◽

Oral Drug Delivery ◽

Cell Model ◽

Oral Drug ◽

Drug Efflux ◽

Inversion Point ◽

Improve Rate

ABSTRACTBackground: The development of appropriate dosage forms for paediatric antiretroviral therapy is key for improved therapeutic outcomes in children. The focus of this study was to improve solubility, dissolution rate, drug release and maintain high drug permeability.Methodology: A nanoemulsion was prepared using emulsion inversion point and evaluated. The nanoemulsion had nevirapine (3% w/w). In vitro drug release studies were performed using dialysis membrane. Permeability studies using the Caco-2 cell model were performed for the formulation.Results: The optimized nevirapine nanoemulsion had a mean droplet size of 36.09±12.27nm, low pdI of 0.598 and zeta potential of -7.87±4.35mV. At pH 2, the nanoemulsion released 76 ± 2 % of nevirapine within 2 h, while at pH 6.4 value representing the small intestine, amount of nevirapine released was 41.6± 4 %. The permeability rate of the nevirapine nanoemulsion was 30.02 x 10-6cm/s and higher than that of propranolol. Efflux ratio was 0.02 indicating low chance of drug efflux occurring.Conclusion: The results showed that a modified liquid drug release formulations of nevirapine could improve rate of dissolution and maintain high permeability and low drug efflux improving bioavailability of nevirapine in vivo.

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In-Vitro Functionality of Clozapine Biphasic Release Minitablet Using Advanced Statistical Tools

Drug Delivery Letters ◽

10.2174/2210303111666210412163605 ◽

2021 ◽

Vol 11 ◽

Author(s):

Hardik Rana ◽

Rushikesh Chaudhari ◽

Vaishali Thakkar ◽

Tejal Gandhi

Keyword(s):

Drug Release ◽

Sustained Release ◽

Ethyl Cellulose ◽

Dosage Form ◽

Immediate Release ◽

Solid Dosage Form ◽

Solid Dosage ◽

Precipitation Inhibitor

Background: The better control of the drug release with immediate effect is the major concern to achieve better therapeutic action and patient compliance. The failure of the solid dispersion complex during storage as well as in-vivo is another concern for the oral solid dosage form. Objective: The prime objective of the present study was to optimize the biphasic minitablet incorporating quality by design approach using the combination of waxy erodible and water-impermeable excipients. Exploration of Soluplus as a precipitation inhibitor and Dexolve as a solubility enhancer in oral solid dosage form was the secondary objective. Methods: The drug-Excipient compatibility study was assessed by FTIR. Clozapine was chosen as a model drug that has poor aqueous solubility. The complex was formulated using B-cyclodextrin or HP B-CD or Dexolve by kneading method. The screening of solubility enhancers and their amount were performed based on phase solubility study. The precipitation inhibitor was screened as per the parachute effect study. Immediate release minitablets were formulated using a direct compression method using different disintegrating agents. The IR minitablets were evaluated for different evaluation parameters. The sustained release minitablets was formulated by hot-melt granulation technique incorporating the Precirol ATO 5 as a waxy excipient and ethyl cellulose as water impermeable excipient. The SR minitablet was optimized using a central composite design. The amount of Precirol ATO 5 and ethyl cellulose were chosen as independent variables and % drug release at 1, 6, and 10 h was selected as responses. The designed batches were evaluated for different pre and post compressional parameters. The IR and SR minitablets were filled in a capsule as per dose requirement and evaluated for in-vitro drug release. The in-vivo plasma concentration was predicted using the Back calculation of the Wagner – Nelson approach. Results: Drug – Excipient study revealed that no significant interaction was observed. Dexolve was screened as a solubility enhancer for the improvement of the solubility of clozapine. The Soluplus was chosen as a precipitation inhibitor from the parachute effect study. The immediate-release tablet was formulated using Prosolv EASYtab SP yield less disintegration time with better flowability. The sustained release mini-tablet was formulated using Precirol ATO 5 and ethyl cellulose. Two-dimensional and three-dimensional plots were revealed the significant effect of the amount of Precirol ATO 5 and ethyl cellulose. The overlay plot locates the optimized region. The in-vitro drug release study revealed the desired drug release of the final combined formulation. The in-vivo plasma concentration-time confirms the drug release up to 12h. Conclusion: The biphasic mini-tablets were formulated successfully for better control of drug release leads to high patient compliance. The use of soluplus as a precipitation inhibitor is explored in the oral solid dosage form for a poorly aqueous drug. Prosolv EASYtab SP was incorporated in the formulation as super disintegrant. The amount of Precirol ATO 5 and ethyl cellulose had a significant effect on drug release in sustained-release minitablet. The approach can be useful in the industry.

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In Vitro and In Vivo Test Methods for the Evaluation of Gastroretentive Dosage Forms

Pharmaceutics ◽

10.3390/pharmaceutics11080416 ◽

2019 ◽

Vol 11 (8) ◽

pp. 416 ◽

Cited By ~ 3

Author(s):

Schneider ◽

Koziolek ◽

Weitschies

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Oral Drug Delivery ◽

Test Methods ◽

Delivery Systems ◽

Oral Drug ◽

Gastrointestinal Physiology ◽

In Vivo Test

More than 50 years ago, the first concepts for gastroretentive drug delivery systems were developed. Despite extensive research in this field, there is no single formulation concept for which reliable gastroretention has been demonstrated under different prandial conditions. Thus, gastroretention remains the holy grail of oral drug delivery. One of the major reasons for the various setbacks in this field is the lack of predictive in vitro and in vivo test methods used during preclinical development. In most cases, human gastrointestinal physiology is not properly considered, which leads to the application of inappropriate in vitro and animal models. Moreover, conditions in the stomach are often not fully understood. Important aspects such as the kinetics of fluid volumes, gastric pH or mechanical stresses have to be considered in a realistic manner, otherwise, the gastroretentive potential as well as drug release of novel formulations cannot be assessed correctly in preclinical studies. This review, therefore, highlights the most important aspects of human gastrointestinal physiology and discusses their potential implications for the evaluation of gastroretentive drug delivery systems.

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Formulation and in vitro Evaluation of Glimepiride Sustained Release Tablets: Comparison with Immediate Release Tablets

Bangladesh Pharmaceutical Journal ◽

10.3329/bpj.v18i2.24315 ◽

2015 ◽

Vol 18 (2) ◽

pp. 157-162

Author(s):

Samira Karim ◽

Mohiuddin Ahmed Bhuiyan ◽

Md Sohel Rana

Keyword(s):

Sustained Release ◽

Immediate Release ◽

Pharmaceutical Journal ◽

In Vitro Dissolution ◽

Release Formulation ◽

Sustained Release Formulation ◽

Zero Order Kinetics ◽

Weight Variation ◽

Sustained Release Tablets

This work aims at the design of a sustained release formulation of glimepiride which is currently available in the treatment of type 2 diabetes mellitus and to investigate the effect of polymers on the release profile of glimepiride. Glimepiride sustained release tablets were prepared by direct compression method using different ratios of various release retarding polymers such as carbopol, ethyl cellulose, methocel K4 MCR, methocel K15 MCR, methocel K100 MCR and xanthum gum. These formulations were also compared with glimepiride immediate release tablets. The prepared tablets were subjected to various physical parameter tests including weight variation, friability, hardness, thickness, diameter, etc. In vitro dissolution studies of the formulations were done at pH 6.8 in phosphate buffer using USP apparatus 2 (paddle method) at 50 rpm. The percent releases of all the formulations (30) were 73.11%- 98.76% after 8 hours. The release pattern followed zero order kinetics and the release of the drug was hindered by the polymers used in the study. On the other hand, 100% drug was released within 1 hour from the immediate release tablet of glimepiride. The study reveals that the polymers used have the capacity to retard the release of the drug from the sustained release tablets and the more is the amount of the polymer in the formulation the less is the release of drug showing more retardation of drug release.Bangladesh Pharmaceutical Journal 18(2): 157-162, 2015

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