Formulation and Evaluation of Fast Dissolving Gliclazide Tablets by Complexation with Hydroxypropyl-β-Cyclodextrin

2014 ◽  
Vol 7 (1) ◽  
pp. 2399-2405
Author(s):  
Adel M Aly ◽  
Khaled M. Al-Akhali ◽  
Hesham Alrefaey ◽  
Mahmoud A. Shaker
Keyword(s):  
Dissolution Rate ◽  
Spray Drying ◽  
Inclusion Complexes ◽  
In Vitro Release ◽  
Hypoglycemic Effect ◽  
Scanning Calorimetry ◽  
Molar Ratios ◽  
Market Product

Gliclazide (GZ) is practically insoluble in water and its bioavailability is limited by dissolution rate. The aim of the present study was to enhance the dissolution rate and bioavailability of GZ by complexation with hydroxypropyl (HP)-β-cyclodextrin (CD) applying three different methods; physical mixing, kneading technique and spray drying technique.  Also, to evaluate the dissolution rate and the hypoglycemic effect of the prepared complexes, in comparison with the GZ market product (Glizide tablets) in Saudi market. The produced complexes were characterized and evaluated using Differential Scanning Calorimetry (DSC), X-ray Diffractometry (XRD), Scanning Electron Microscope (SEM) and the in vitro release studies. All the methods of preparation of complexes were found to be effective in improving the solubility of gliclazide in comparison with the commercial product (Glizide tablets). The formation of inclusion complexes was evident in these formulations as shown by DSC and XRD studies. The inclusion complexes prepared by spray drying method in 1:1 molar ratios were the most effective method for improving the solubility of GZ. The in-vivo hypoglycemic effect of the complexed GZ-HP-β-CD prepared by spray drying significantly improved the biological performance and therapeutic efficacy of the drug compared to Glizide market product.  

scholarly journals Effect of Sulindac Binary System on In Vitro and In Vivo Release Profiles: An Assessment of Polymer Type and Its Ratio

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Gamal A. Shazly
Keyword(s):  
Dissolution Rate ◽  
In Vitro Release ◽  
Weight Ratio ◽  
Crystal Habit ◽  
Scanning Calorimetry ◽  
Peg 6000 ◽  
Anti Inflammatory ◽  
Inflammatory Effect

The bioavailability of sulindac (SDC), a nonsteroidal anti-inflammatory drug, is low due to poor aqueous solubility and poor dissolution rate. For this reason it is necessary to enhance the solubility and enhance dissolution of the drug by dispersing SDC in polyethylene glycols 6000 (PEG 6000) and polyvinyl pyrrolidone 40000 (PVP 40000) matrices using the coevaporation technique. Studying the influence of SDC to polymer ratio on drug content, percent yield, particle size, and in vitro release was performed. Differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy were used to characterize any change in crystal habit of SDC in the prepared formulae. The anti-inflammatory effect of SDC was studied using the hind paw edema model. It was found that incorporation of SDC in PEG 6000 and PVP 40000 matrices resulted in improving the dissolution rate, which was found to depend on the polymer and its weight ratio of the drug. It is clearly obvious that the dissolution rate was remarkably improved in drug PVP 40000 molecular dispersions when compared to drug PEG 6000 systems. Solid dispersion of SDC in PEG and PVP improved the anti-inflammatory effect of SDC and it was found that formula SDV5 exhibited a more pronounced inhibition of swelling than other formulae.

Fenofibrate Solid Dispersion for Improving Oral Bioavailability: Preparation, and Characterization and in vivo Evaluation

2020 ◽  
Vol 13 (5) ◽  
pp. 5102-5109
Author(s):  
Venu Madhav K ◽  
Somnath De ◽  
Chandra Shekar Bonagiri ◽  
Sridhar Babu Gummadi
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Solid Dispersions ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
Scanning Calorimetry ◽  
In Vivo Evaluation

Fenofibrate (FN) is used in the treatment of hypercholesterolemia. It shows poor dissolution and poor oral bioavailability after oral administration due to high liphophilicity and low aqueous solubility. Hence, solid dispersions (SDs) of FN (FN-SDs) were develop that might enhance the dissolution and subsequently oral bioavailability. FN-SDs were prepared by solvent casting method using different carriers (PEG 4000, PEG 6000, β cyclodextrin and HP β cyclodextrin) in different proportions (0.25%, 0.5%, 0.75% and 1% w/v). FN-SDs were evaluated solubility, assay and in vitro release studies for the optimization of SD formulation. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) analysis was performed for crystalline and morphology analysis, respectively. Further, optimized FN-SD formulation evaluated for pharmacokinetic performance in Wistar rats, in vivo in comparison with FN suspension.  From the results, FN-SD3 and FN-SD6 have showed 102.9 ±1.3% and 105.5±3.1% drug release, respectively in 2 h. DSC and PXRD studies revealed that conversion of crystalline to amorphous nature of FN from FT-SD formulation. SEM studies revealed the change in the orientation of FN when incorporated in SDs. The oral bioavailability FN-SD3 and FN-SD6 formulations exhibited 2.5-folds and 3.1-folds improvement when compared to FN suspension as control. Overall, SD of FN could be considered as an alternative dosage form for the enhancement of oral delivery of poorly water-soluble FN.

scholarly journals PREPARATION AND CHARACTERIZATION OF NANOCRYSTALS FOR SOLUBILITY AND DISSOLUTION RATE ENHANCEMENT OF PALIPERIDONE USING DIFFERENT HYDROPHILIC CARRIERS: IN VITRO-IN VIVO STUDY

2018 ◽  
Vol 11 (4) ◽  
pp. 393
Author(s):  
Moon Rajkumar ◽  
Gattani Surendra
Keyword(s):  
Dissolution Rate ◽  
Antipsychotic Agent ◽  
Aqueous Solubility ◽  
In Vivo Study ◽  
Scanning Calorimetry ◽  
Antisolvent Precipitation ◽  
Enhanced Solubility ◽  
Pure Drug

 Objective: The objective of this study was to increase the solubility and dissolution rate of paliperidone (PAL) by preparing its nanocrystals using different hydrophilic carriers by antisolvent precipitation technique.Methods: The nanoparticles (NP) were characterized for aqueous solubility, drug content, Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, particle size, and in vitro-in vivo analysis.Results: The results showed improved solubility and dissolution rate of NPs when compared to pure drug and physical mixture (PM). Solubility data showed a linear graph giving an indication that there is a gradual increase in the solubility profile of the drug with an increase in concentration of the carriers. At highest concentration, the solubility of NPs with Plasdone S630, Povidone K-25, and PVP K-30 found to be increased by 12 folds, 9 folds and 6 folds, respectively, as compared to pure drug. The release profile of NPs with Plasdone S630 in terms of dissolution efficiency at 60 min (DE60), initial dissolution rate (IDR), amount release in 15 min (Q15 min), and time for 75% release (t75%) shows better results when compared to pure drug, PM, and also NPs with povidone 25 and povidone 30. In vivo study reveals that optimized NPs elicited significant induction of cataleptic behavior which is the indication of antipsychotic agent(s) effect.Conclusion: The process antisolvent precipitation under constant stirring may be a promising method to produce stable PAL NPs with markedly enhanced solubility and dissolution rate due to nanonization with the increased surface area, improved wettability, and reduced diffusion pathway.

scholarly journals DEVELOPMENT OF RITONAVIR LOADED NANOPARTICLES: IN VITRO AND IN VIVO CHARACTERIZATION

2018 ◽  
Vol 11 (3) ◽  
pp. 284
Author(s):  
Pravin S Patil ◽  
Shashikant C Dhawale
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Dissolution Rate ◽  
Drug Carrier ◽  
Entrapment Efficiency ◽  
Significant Rise ◽  
Scanning Calorimetry ◽  
In Vitro Drug Release

 Objective: The purpose of the present investigation was to develop a nanosuspension to improve dissolution rate and oral bioavailability of ritonavir.Methods: Extended-release ritonavir loaded nanoparticles were prepared using the polymeric system by nanoprecipitation technique. Further, the effect of Eudragit RL100 (polymeric matrix) and polyvinyl alcohol (surfactant) was investigated on particle size and distribution, drug content, entrapment efficiency, and in vitro drug release from nanosuspension where a strong influence of polymeric contents was observed. Drug-excipient compatibility and amorphous nature of drug in prepared nanoparticles were confirmed by Fourier transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction studies, respectively.Results: Hydrophobic portions of Eudragit RL100 could result in enhanced encapsulation efficiency. However, increase in polymer and surfactant contents lead to enlarged particle size proportionately as confirmed by transmission electron microscopy. Nanosuspension showed a significant rise in dissolution rate with complete in vitro drug release as well as higher bioavailability in rats compared to the pure drug.Conclusion: The nanoprecipitation technique used in present research could be further explored for the development of different antiretroviral drug carrier therapeutics.

scholarly journals Self-Assembled Casein Nanoparticles Loading Triptolide for the Enhancement of Oral Bioavailability

2020 ◽  
Vol 15 (8) ◽  
pp. 1934578X2094835
Author(s):  
Chengxia Liu ◽  
Ting-ting Jiang ◽  
Zhi-xiang Yuan ◽  
Yu Lu
Keyword(s):  
Self Assembly ◽  
Oral Bioavailability ◽  
In Vitro Release ◽  
Area Under The Curve ◽  
Entrapment Efficiency ◽  
Infrared Spectrometry ◽  
Scanning Calorimetry ◽  
Insoluble Drugs

Triptolide (TP), a broad-spectrum antitumor drug, has very poor solubility and oral bioavailability, which limits its clinical use. Compared with conventional formulations of TP, a casein (Cas)-based drug delivery system has been reported to have significant advantages for the improvement of solubility and bioavailability of insoluble drugs. In this paper, we report the successful preparation of TP-loaded Cas nanoparticles (TP-Cas) using the self-assembly characteristics of Cas in water and the optimization of the formulation by evaluation of entrapment efficiency (EE) and loading efficiency (LE). Dynamic light scattering, transmission electron microscopy, Fourier-transform infrared spectrometry, X-ray diffractometry (XRD), and differential scanning calorimetry (DSC) was adopted to characterize the TP-Cas. Results showed that the obtained TP-Cas were approximately spherical with a particle size of 128.7 ± 11.5 nm, EE of 72.7 ± 4.7 %, and LE of 8.0% ± 0.5%. Furthermore, in vitro release behavior of TP-Cas in PBS (pH = 7.4) was also evaluated, showing a sustained-release profile. Additionally, an in vivo study in rats displayed that the mean plasma concentration of TP after oral administration of TP-Cas was significantly higher than that treated with TP oral suspension. The C max value for TP-Cas (8.0 ± 4.4 μg/mL) was significantly increased compared with the free TP (0.9 ± 0.3 μg/mL). Accordingly, the area under the curve (AUC0-8) of TP-Cas was 2.8 ± 0.8 mg/L·h, 4.3-fold higher than that of TP suspension (0.6 ± 0.1 mg/L·h). Therefore, it can be concluded that TP-Cas enhanced the absorption and improved oral bioavailability of TP. Taking the good oral safety of Cas into consideration, TP-Cas should be a more promising preparation of TP for clinical application.

scholarly journals Tripling the Bioavailability of Rosuvastatin Calcium Through Development and Optimization of an In-Situ Forming Nanovesicular System

Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 275 ◽  
Author(s):  
Ibrahim Elsayed ◽  
Rania Moataz El-Dahmy ◽  
Ahmed Hassen Elshafeey ◽  
Nabaweya Abdelaziz Abd El Gawad ◽  
Omaima Naim El Gazayerly
Keyword(s):  
Dissolution Rate ◽  
Oral Bioavailability ◽  
Entrapment Efficiency ◽  
In Situ Forming ◽  
Market Product ◽  
Simple Step ◽  
Rosuvastatin Calcium

In situ forming nanovesicular systems (IFNs) were prepared and optimized to improve Rosuvastatin calcium (RC) oral bioavailability through increasing its solubility and dissolution rate. The IFN was composed of Tween® 80 (T80), cetyl alcohol (CA), in addition to mannitol or Aerosil 200. A single simple step was adopted for preparation, then the prepared formulations were investigated by analyzing their particle size (PS), polydispersity index (PDI), Zeta potential (ZP), entrapment efficiency (EE), and flowability properties. D-optimal design was applied to choose the optimized formulations. The maximum desirability values were 0.754 and 0.478 for the optimized formulations containing 0.05 g CA, 0.18 g T80, and 0.5 g mannitol (OFM) or Aerosil (OFA), respectively. In vitro drug release from the optimized formulations showed a significantly faster dissolution rate when compared to the market product. In vivo performance of the optimized formulations in rabbits was investigated after filling them into enteric-coated capsules. Ultimately, OFA formulation achieved a 3 times increase in RC oral bioavailability in comparison with the market product, supporting the hypothesis of considering IFNs as promising nanocarriers able to boost the bioavailability of BCS class II drugs.

scholarly journals Preparation and Characterization of Spherical Amorphous Solid Dispersion with Amphotericin B

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 235 ◽  
Author(s):  
Lyes Mehenni ◽  
Malika Lahiani-Skiba ◽  
Guy Ladam ◽  
François Hallouard ◽  
Mohamed Skiba
Keyword(s):  
Amphotericin B ◽  
Solid Dispersion ◽  
In Vitro Release ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersion ◽  
Scanning Calorimetry ◽  
New Generation ◽  
Powder Aerosols

In the present study, new polymer microspheres of amphotericin B (AmB) were prepared by a spray drying technique using cyclodextrin polymers (Poly-CD) to improve the solubility and dissolution of AmB, to prevent in vivo toxic AmB aggregations. Formulations were characterized through scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermal analysis, Raman spectroscopy, particle size, drug purity test and in vitro release studies. The analysis indicated that the chemical structure of AmB remained unchanged in the amorphous solid dispersion, but the structure was changed from crystalline to amorphous. AmB was completely release from such optimized formulations in dissolution media in 40 min. This work may contribute to a new generation of spherical amorphous solid dispersion using a cyclodextrin polymer, which has implications for the possibility of drug development for oral utilization or as powder aerosols for pulmonary administration.

INVESTIGATION OF SOLUBILITY ENHANCEMENT OF PRASUGREL HYDROCHLORIDE: NANOSUSPENSIONS AND CYCLODEXTRIN INCLUSION COMPLEXES

INDIAN DRUGS ◽  
2014 ◽  
Vol 51 (02) ◽  
pp. 29-38
Author(s):  
R. K Devara ◽  
◽  
P. Reddipogu ◽  
S Kumar ◽  
B. Rambabu ◽  
...  
Keyword(s):  
Dissolution Rate ◽  
Inclusion Complexes ◽  
Oral Bioavailability ◽  
Oral Absorption ◽  
In Vitro Dissolution ◽  
Precipitation Method ◽  
Formulation Development ◽  
Pure Drug

The objective of this study was to investigate nanosuspensions, hydroxypropyl-β-cyclodextrin (HPβCD) complexes and SLS powders for enhancing the solubility and dissolution rate of Prasugrel HCl (PHCl) so as to reduce the fluctuations in its oral bioavailability. PHCl nanosuspensions were prepared using evaporative precipitation method. HPβCD inclusion complexes of PHCl were prepared using physical mixture, co-evaporation and kneading methods. Powders of the pure drug with different SLS amounts were prepared. The formulations were characterized using techniques such as powder x-ray diffractometry, scanning electron microscopy, in vitro dissolution and in vivo absorption in rats. To further aid in the betterment of development of nevirapine nanosuspension, in vitro in vivo correlation (IVIVC) was established using deconvolution technique. Nanosuspensions and HPβCD inclusion complexes of PHCl were successfully prepared. The dissolution rate and oral absorption of PHCl in the form of nanosuspensions was significantly higher than that of HPβCD complexes, SLS powders as well as pure drug. All the techniques investigated in this study can be used to enhance dissolution rate and oral absorption of prasugrel HCl and thus can reduce the fluctuations in its oral bioavailability. Nanosuspensions demonstrated to be better and superior technique when compared to other techniques investigated in enhancing oral bioavailability of PHCl. IVIVC that could aid in further formulation development of PHCl nanosuspension was successfully developed using a deconvolution approach.

scholarly journals Preparation and Preliminary Evaluation of Novel β-Cyclodextrin/IUDR Prodrug Formulations

2008 ◽  
Vol 11 (2) ◽  
pp. 32 ◽  
Author(s):  
Leonard I. Wiebe ◽  
Xiao-Hong Yang ◽  
Shradha Singh ◽  
Jim Diakur
Keyword(s):  
Inclusion Complexes ◽  
In Vivo Studies ◽  
Preliminary Evaluation ◽  
Target Tissue ◽  
Molar Ratios ◽  
Nmr Spectrometry ◽  
Complex Approach ◽  
The Stability

PURPOSE. Iododeoxyuridine (IUdR) has a very short in vivo half-life and consequently achieves low target-tissue concentrations with concomitant lower efficacy than would be predicted from in vitro studies. This work reports the preparation of IUdR:?-cyclodextrin (?-CyD) inclusion complexes designed to reduce in vivo inactivation of IUdR. METHODS. IUdR was derivatized with either 1-adamantanecarbonyl chloride or 4-(1-adamantyl-carbamoyl)butanoic acid, to prepare 5’-O-(1-adamantoyl)-5-iodo-2’-deoxyuridine 1 and 5’-O-(4-(1-adamantylcarbamoyl)butoyl)-5-iodo-2’-deoxy-uridine 4, respectively. ?-CyD complexes 5 and 6 were formed by vigorous stirring of 1:1 solutions of ?-CyD and 1 or 4, respectively, in D2O under argon. Complexation was inferred from DSC, powder x-ray diffractometry and NMR spectrometry. The dissociation of 5 in water and under cholesterol challenge, and the effect of complexation on the stability of 1 was determined by incubation in plasma. RESULTS. IUdR coupling with adamantanecarbonyl chloride proceeded smoothly to afford 1 (69 %) and the di-substituted derivative, 3’,5’-di-O-(1-adamantoyl)-5-iodo-2’-deoxyuridine 2 (8 %); 4 was obtained in 42 % yield. The formation of 1:1 complexes 5 and 6 was inferred from NMR chemical shift data. In serum, 1 was 90 % hydrolyzed to IUdR in 30 min, compared to 10 % hydrolysis of 1 to IUdR when from complex 5. CONCLUSIONS. Inclusion complexes were formed between ?-CyD and adamantamine-IUdR conjugates at 1:1 molar ratios. The complex 5 was resistant to dissociation by cholesterol challenge, and 5 was more slowly converted to IUdR than non-complexed 1. In vivo studies are required to further exploit the ?-CyD inclusion complex approach for improved delivery of nucleoside derivatives.

scholarly journals Preparation and characterization of artemether inclusion complexes with hydroxypropyl-β-cyclodextrin

2017 ◽  
Vol 16 (10) ◽  
pp. 2359-2364
Author(s):  
Zwanden Sule Yahaya ◽  
Kenneth C. Ofokansi ◽  
Suzane T. Allagh ◽  
Pat G. Bhatia
Keyword(s):  
Complex Formation ◽  
Inclusion Complex ◽  
Dissolution Rate ◽  
Inclusion Complexes ◽  
In Vitro Dissolution ◽  
Phase Solubility ◽  
Inclusion Complex Formation ◽  
Scanning Calorimetry ◽  
Ft Ir

Purpose: To investigate experimentally the inclusion of artemether into the cavity of  hydroxypropyl-β-cyclodextrin and examine its effect on the solubility and dissolution rate of the drug.Methods: Inclusion complexes of artemether with hydroxypropyl-β-cyclodextrin of molar ratios 1:1, 1:2 and 1:3 were prepared using the kneading method. Phase solubility analysis and in vitro dissolution studies were utilized in evaluating the influence of inclusion complex formation on the solubility and dissolution rate of the drug. The complexes were characterized using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The inclusion complex containing equimolar concentrations of artemether and hydroxypropyl-β-cyclodextrin was then formulated into tablets via direct compression and  evaluated for various pharmaceutical characteristics including hardness, friability, absolute drug content and comparative in vitro dissolution profiles with some  commercially available brands of artemether.Results: The phase solubility diagram for the formed complexes in water at 37 oC indicated a linear curve soluble complex system (referred to as the AL system), and a stability constant (KC) value of 143 M-1. Evidence consistent with inclusion complex formation was obtained using FT-IR and DSC. The formulated inclusion complex tablets exhibited a higher rate of dissolution than the pure drug and commercial brands, showing 3.9-, 1.8- and 1.6-fold increases, respectively, over a period of 15 min.Conclusion: Inclusion complexation of artemether with hydroxypropyl-β-cyclodextrin is a promising approach to enhance the solubility and dissolution rate of the drug.Keywords: Artemether, 2-Hydroxypropyl-β-cyclodextrin, Dissolution, Solubility enhancement, Inclusion complex

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