Release mechanism based on polymer-drug dissolution and stability studies of paracetamol solid dispersion

Purposes: Aims of this study are dissolution enhancement of a poorly water-soluble drug by nano-sized solid dispersion and investigation of machenism of drug release from the solid dispersion. A drug for osteoporosis treatment was used as the model drug in the study. Methods: melting method was used to prepare the solid dispersion. Drug dissolution rate was investigated at pH 1.2 and pH 6.8. Drug crystallinity was studied using differential scanning calorimetric and powder X-ray diffraction. In addition, droplet size and contact angle of drug were determined to elucidate mechanism of drug release. Results: Drug dissolution from the solid dispersion was significantly increased at pH 1.2 and pH 6.8 as compared to pure drug. Drug crystallinity was changed to partially amorphous. Also dissolution enhancement of drug was due to the improved wettability. The droplet size of drug was in the scale of nano-size when solid dispersion was dispersed in dissolution media. Conclusions: nano-sized solid dispersion in this research was a successful preparation to enhance bioavailability of a poorly water-soluble drug by mechanisms of crystal changes, particle size reduction and increase of wet property.

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Formulation Design and Optimization of Repaglinide Solid Dispersions by Central Composite Design

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2018.11.6.7 ◽

2018 ◽

Vol 11 (6) ◽

pp. 4337-4348

Author(s):

Bhikshapathi D. V. R. N. ◽

Srinivas I

Keyword(s):

Central Composite Design ◽

Dissolution Rate ◽

Solid Dispersion ◽

Solid Dispersions ◽

Solvent Evaporation ◽

Release Mechanism ◽

Solvent Evaporation Method ◽

Onset Of Action ◽

Evaporation Method ◽

Central Composite

Repaglinide is a pharmaceutical drug used for the treatment of type II diabetes mellitus, it is characterized with poor solubility which limits its absorption and dissolution rate and delays onset of action. In the present study, immediate release solid dispersion of repaglinide was formulated by solvent evaporation technique. Repaglinide solid dispersions were prepared using PEG 8000, Pluronic F 127 and Gelucire 44/14 by solvent evaporation method. A 3-factor, 3-level central composite design employed to study the effect of each independent variable on dependent variables. FTIR studies revealed that no drug excipient interaction takes place. From powder X-ray diffraction (p-XRD) and by scanning electron microscopy (SEM) studies it was evident that polymorphic form of repaglinide has been converted into an amorphous form from crystalline within the solid dispersion formulation. The correlation coefficient showed that the release profile followed Higuchi model anomalous behavior and hence release mechanism was indicative of diffusion. The obtained results suggested that developed solid dispersion by solvent evaporation method might be an efficacious approach for enhancing the solubility and dissolution rate of repaglinide.

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Development of Controlled-Release Carbamide Peroxide Loaded Nanoemulgel for Tooth Bleaching: In Vitro and Ex Vivo Studies

Pharmaceuticals ◽

10.3390/ph14020132 ◽

2021 ◽

Vol 14 (2) ◽

pp. 132

Author(s):

Siriporn Okonogi ◽

Adchareeya Kaewpinta ◽

Sakornrat Khongkhunthian ◽

Pisaisit Chaijareenont

Keyword(s):

Drug Release ◽

Solid Dispersion ◽

Solid Dispersions ◽

Tooth Bleaching ◽

Polymer Mixture ◽

Release Mechanism ◽

Burst Release ◽

Order Kinetic ◽

Carbamide Peroxide ◽

Periodontal Tissues

Burst release of carbamide peroxide (CP) from traditional hydrogels causes severe inflammation to periodontal tissues. The present study explores the development of a novel CP nanoemulgel (CP-NG), an oil-in-water nanoemulsion-based gel in which CP was loaded with a view to controlling CP release. CP solid dispersions were prepared, using white soft paraffin or polyvinylpyrrolidone-white soft paraffin mixture as a carrier, prior to formulating nanoemulsions. It was found that carrier type and the ratio of CP to carrier affected drug crystallinity. Nanoemulsions formulated from the optimized CP solid dispersions were used to prepare CP-NG. It was found that the ratio of drug to carrier in CP solid dispersions affected the particle size and zeta potential of the nanoemulsions as well as drug release behavior and tooth bleaching efficacy of CP-NG. Drug release from CP-NG followed a first-order kinetic reaction and the release mechanism was an anomalous transport. Drug release rate decreased with an increase in solid dispersion carriers. CP-NG obtained from the solid dispersion with a 1:1 ratio of CP to the polymer mixture is suitable for sustaining drug release with high tooth bleaching efficacy and without reduction of enamel microhardness. The developed CP-NG is a promising potential tooth bleaching formulation.

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The Development and Optimization of Hot-Melt Extruded Amorphous Solid Dispersions Containing Rivaroxaban in Combination with Polymers

Pharmaceutics ◽

10.3390/pharmaceutics13030344 ◽

2021 ◽

Vol 13 (3) ◽

pp. 344

Author(s):

Jong-Hwa Lee ◽

Hyeong Sik Jeong ◽

Jong-Woo Jeong ◽

Tae-Sung Koo ◽

Do-Kyun Kim ◽

...

Keyword(s):

Drug Delivery ◽

Dissolution Rate ◽

Solid Dispersion ◽

Oral Drug Delivery ◽

Amorphous Solid ◽

Drug Dissolution ◽

Oral Drug ◽

Amorphous Solid Dispersion ◽

Screw Speed ◽

Hot Melt

Rivaroxaban (RXB), a novel oral anticoagulant that directly inhibits factor Xa, is a poorly soluble drug belonging to Biopharmaceutics Classification System (BCS) class II. In this study, a hot-melt extruded amorphous solid dispersion (HME-ASD) containing RXB is prepared by changing the drug:polymer ratio (Polyvinylpyrrolidione-vinyl acetate 64, 1:1–1:4) and barrel temperature (200–240 °C), fixed at 20% of Cremophor® RH 40 and 15 rpm of the screw speed, using the hot-melt extruding technique. This study evaluates the solubility, dissolution behavior, and bioavailability for application to oral drug delivery and optimizes the formulation of rivaroxaban amorphous solid dispersion (RXB-ASD). Based on a central composite design, optimized RXB-ASD (PVP VA 64 ratio 1:4.1, barrel temperature 216.1 °C, Cremophor® RH 40 20%, screw speed 15 rpm) showed satisfactory results for dependent variables. An in vitro drug dissolution study exhibited relatively high dissolution in four media and achieved around an 80% cumulative drug release in 120 min. Optimized RXB-ASD was stable under the accelerated condition for three months without a change in crystallinity and the dissolution rate. A pharmacokinetic study of RXB-ASD in rats showed that the absorption was markedly increased in terms of rate and amount, i.e., the systemic exposure values, compared to raw RXB powder. These results showed the application of quality by design (QbD) in the formulation development of hot-melt extruded RXB-ASD, which can be used as an oral drug delivery system by increasing the dissolution rate and bioavailability.

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Formulation and evaluation of proniosome loaded sertaconazole nitrate for topical application

International Journal of Life Science Research Archive ◽

10.53771/ijlsra.2021.1.2.0060 ◽

2021 ◽

Vol 1 (2) ◽

pp. 023-037

Author(s):

Shailaja D ◽

Latha K ◽

Manasa D ◽

Shirisha A ◽

Padmavathi R ◽

...

Keyword(s):

Ex Vivo ◽

Release Kinetics ◽

Skin Irritation ◽

Water Soluble ◽

Ionic Surfactants ◽

Release Mechanism ◽

Stability Studies ◽

Zero Order Release ◽

Poorly Soluble

Proniosomal technology is a novel solution for poorly soluble drugs. Proniosomes are water-soluble carrier particles which are coated with non-ionic surfactants. Proniosomal gels were prepared by coacervation phase separation method using non-ionic surfactants, lipid carriers and cholesterol as a membrane stabilizer. FTIR compatibility studies revealed that the drug and excipients were compatible. All formulations were evaluated for pH, drug content, extrudability, spreadability, viscosity, in-vitro, ex-vivo, skin irritation and stability studies. Among formulations prepared, F80H1 has shown higher % EE (83.02) and least diffusion through dialysis membrane i.e., 17.68%. With ex-vivo studies, F80H1 formulation has shown highest skin deposition and lower flux of sertaconazole nitrate through the rat skin. F80H1 was selected as final optimized formulation. F80H1 exhibited good stability and SEM studies revealed that the vesicles were spherical in shape. The optimized formulation was found to follow zero order release kinetics and korsmeyer-peppas release mechanism. F80H1 found to be non-irritant and stable from skin irritation and stability studies.

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Development of extended-release solid dispersion granules of tacrolimus: evaluation of release mechanism and human oral bioavailability

Journal of Pharmacy and Pharmacology ◽

10.1111/jphp.12804 ◽

2017 ◽

Vol 69 (12) ◽

pp. 1697-1706 ◽

Cited By ~ 4

Author(s):

Daisuke Tsunashima ◽

Kazunari Yamashita ◽

Ken-ichi Ogawara ◽

Kazuhiro Sako ◽

Tadashi Hakomori ◽

...

Keyword(s):

Solid Dispersion ◽

Oral Bioavailability ◽

Extended Release ◽

Release Mechanism

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Preparation, characterization and evaluation of the in vivo trypanocidal activity of ursolic acid-loaded solid dispersion with poloxamer 407 and sodium caprate

Brazilian Journal of Pharmaceutical Sciences ◽

10.1590/s1984-82502015000100011 ◽

2015 ◽

Vol 51 (1) ◽

pp. 101-109 ◽

Cited By ~ 12

Author(s):

Josimar Oliveira Eloy ◽

Juliana Saraiva ◽

Sérgio de Albuquerque ◽

Juliana Maldonado Marchetti

Keyword(s):

Ursolic Acid ◽

Solid Dispersion ◽

Oral Absorption ◽

Solid Dispersions ◽

Poloxamer 407 ◽

Drug Dissolution ◽

Limiting Factors ◽

Sodium Caprate ◽

Trypanocidal Activity

Ursolic acid is a promising candidate for treatment of Chagas disease; however it has low aqueous solubility and intestinal absorption, which are both limiting factors for bioavailability. Among the strategies to enhance the solubility and dissolution of lipophilic drugs, solid dispersions are growing in popularity. In this study, we employed a mixture of the surfactants poloxamer 407 with sodium caprate to produce a solid dispersion containing ursolic acid aimed at enhancing both drug dissolution and in vivo trypanocidal activity. Compared to the physical mixture, the solid dispersion presented higher bulk density and smaller particle size. Fourier Transform Infrared Spectroscopy results showed hydrogen bonding intermolecular interactions between drug and poloxamer 407. X-ray diffractometry experiments revealed the conversion of the drug from its crystalline form to a more soluble amorphous structure. Consequently, the solubility of ursolic acid in the solid dispersion was increased and the drug dissolved in a fast and complete manner. Taken together with the oral absorption-enhancing property of sodium caprate, these results explained the increase of the in vivo trypanocidal activity of ursolic acid in solid dispersion, which also proved to be safe by cytotoxicity evaluation using the LLC-MK2 cell line.

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FORMULATION AND EVALUATION OF LIDOCAINE HYDROCHLORIDE CHEWABLE TABLET

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i11.27057 ◽

2018 ◽

Vol 11 (11) ◽

pp. 190

Author(s):

Harshada Anil Kasar ◽

Asish Dev ◽

Subhakanta Dhal

Keyword(s):

Drug Release ◽

Factorial Design ◽

Release Rate ◽

Statistical Models ◽

Drug Dissolution ◽

Lidocaine Hydrochloride ◽

Dissolution Profile ◽

Stability Studies ◽

Drug Release Rate ◽

Chewable Tablets

Objective: The objective of this study was to formulate and optimize a chewable formulation of lidocaine hydrochloride using a 32 factorial design for optimized the superdisintegrant concentration.Methods: Various concentrations of sodium starch glycolate (SSG) (13.33 mg, 26.66 mg, and 40 mg) of superdisintegrant and starch (50 mg, 83 mg, and 116.66 mg) were added in the formulation; nine formulations were prepared according to 32 factorial designs and evaluated. The responses were analyzed for analysis of variance using Design-Expert version 10 software. Statistical models were generated for each response parameter. The models were tested for significance. Procedure to manufacture chewable tablets by direct compression was established.Results: The results show that the presence of a superdisintegrant is desirable for chewable formulation. The best-optimized batch F7 found the batch having starch of amount 116.66 mg and SSG 13.33 mg. All the prepared batches of tablets were within the range. Optimized batch F7 showed drug content 102.46±0.0543, wetting time 18±1.7320, friability 0.65±0.0216, and drug release rate 99.97±0.0124% at the end of 30 min.Conclusion: It can be concluded that 32 full factorial design and statistical models can be successfully used to optimize the formulations, and it was concluded that the trial batch F7 is the optimized formulation which compiles official specifications of chewable tablets. The optimized batch was evaluated for thickness, weight variation, hardness, friability, drug dissolution, and stability study for 3 months. The similarity factor was calculated for comparison of dissolution profile before and after stability studies. After 30 min the drug release rate for batch F7 was 98.97% (Table 6). Hence, the results of stability studies reveal that the developed formulation has good stability.

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OPTIMIZATION OF FORMULATION OF SOLID DISPERSION OF FUROSEMIDE BY FACTORIAL DESIGN

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2020v12i4.36428 ◽

2020 ◽

pp. 43-48

Author(s):

SHARWAREE R. HARDIKAR ◽

SHAKIL S. MULLA

Keyword(s):

Factorial Design ◽

Solid Dispersion ◽

Lepidium Sativum ◽

The Novel ◽

Stability Studies ◽

Lactose Monohydrate ◽

Molecular Dispersion ◽

Rate Of Dissolution ◽

Dispersion Technique ◽

Anhydrous Lactose

Objective: The present study aimed to improve the rate of dissolution of furosemide by solid dispersion technique. Methods: Solid dispersion of furosemide was prepared by using hydrogel isolated from the seeds of Lepidium sativum as a novel carrier by the solvent evaporation method. Solid dispersion was evaluated to study the improvement in the rate of dissolution. Molecular dispersion of furosemide in the novel carrier was studied by DSC and FTIR studies. Solid dispersion was filled in capsules after stability studies and the formulation was optimized by adopting factorial design. Results: Solid dispersion of furosemide exhibited dissolution improvement from 13.54 % (plain furosemide) to 69.12% (solid dispersion) in the first 60 min. Improvement in dissolution efficiency was found to be retained after stability studies. Capsules were filled with the formulation of solid dispersion using two different grades of lactose-α lactose monohydrate and anhydrous lactose and were found stable after stabilization studies. Conclusion: The dissolution improvement of furosemide was attributed to its molecular dispersion in the novel carrier selected for this study. The recrystallization of furosemide was prevented due to intermolecular interaction between the novel carrier and furosemide. This was confirmed by FTIR. Evaluation of the dissolution data of factorial batches was analyzed by ANOVA. Analysis of the data revealed that selected levels of α lactose monohydrate and anhydrous lactose would be useful to navigate design space.

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