Development and Optimization of Atorvastatin Calcium-Cyclodextrin Inclusion Complexed Orally-Disintegrating Tablets with Enhanced Pharmacokinetic and Pharmaco-dynamic Profile

1970 ◽  
Vol 9 (2) ◽  
pp. 3170-3180
Author(s):  
Palem Chinna Reddy ◽  
Narendar Reddy Dudhipala ◽  
Satyanarayana Goda ◽  
Varsha B. Pokharkar
Keyword(s):  
Central Composite Design ◽  
Dissolution Rate ◽  
In Vivo Studies ◽  
Drying Methods ◽  
Phase Solubility ◽  
Dissolution Profile ◽  
Atorvastatin Calcium ◽  
Central Composite ◽  
Spray Dried

The content of the investigation was to study the influence of hydroxy propyl-b-cyclodextrin (HPβCD) complexed oral disintegrating tablets (ODTs) on enhancement of solubility, dissolution rate, pharmacodynamic activity and bioavailability of atorvastatin calcium (AT) by central composite design. Based on preliminary phase solubility studies, solubility was linearly increased and followed AL-type profile. Solid complexes were prepared by physical mixing, kneading, freeze and spray drying methods. Spray-dried product showed higher solubility and dissolution rate than other complexes. Amount of drug (X1), amount of HPβCD (X2) and amount of supradisintegrant (X3) as independent and solubility (Y1), disintegration time (Y2) and percent drug release in 15 min (Q15, Y3) as dependent responses. Drug- HPβCD complex formation was confirmed by FTIR, DSC and XRD. AT-HPβCD ODTs were developed and evaluated for physico-chemical properties, stability and dissolution rate. Further, in vivo pharmacokinetic and pharmacodynamic studies were performed in rat model. The statistically optimized formulation showed 0.817 ± 0.06 mg/ml of solubility, 54 ± 2 sec of DT and 69 ± 2.4 % of Q15. The physical stability was studied for 6 months. No significant changes were detected in dissolution profile and drug content of tablets after 6 months during the stability studies. The in vivo studies of spray dried complexed tablets compared to AT in rats revealed that 3.3-folds improvement in oral bioavailability and there was significant reduction (p<0.01) in cholesterol and triglyceride levels and significant improvement (p<0.01) in HDL level. The results conclusively demonstrated that the AT-HPbCD-ODT could be prepared with improved solubility and hypolipidemic activity by using central composite design.

scholarly journals Design expert assisted mathematical optimization of solubility and study of fast disintegrating tablets of Lercanidipine Hydrochloride

2019 ◽  
Vol 9 (1-s) ◽  
pp. 172-180
Author(s):  
Seema Saini ◽  
Rajeev Garg
Keyword(s):  
Dissolution Rate ◽  
Solid Dispersion ◽  
Solid Dispersions ◽  
Mathematical Optimization ◽  
Statistical Design ◽  
In Vivo Studies ◽  
Dissolution Profile ◽  
Fast Disintegrating Tablets ◽  
Lercanidipine Hydrochloride

90% of drugs being researched today, posses poor solubility setback which inturn renders  the drug with slower rate of absorption from the buccal route; hence dissolution is the rate limiting step for such lipophilic drugs. So, there is a need to keep a check on the dissolution profile of these drugs to ensure maximum therapeutic utilization. The dissolution rate therefore becomes a primary factor which governs the rate and extent of its absorption. Enormous work is being performed in the field of enhancement of solubility and dissolution behaviour of such drugs. Advancements and innovations have developed solid dispersion (SD) technique as the novel method for the solubility enhancement. Precision of dosing and patient's compliance is a crucial prerequisite for the management of chronic Antihypertensive treatment, So there arised a need to formulate a system which should resolve the difficulties associated with conventional tablets. This issue can be better tackled with the formulation of orally fast disintegrating tablets. The aim of the present study was to improve the solubility and dissolution rate of Lercanidipine hydrochloride (LRH) by formulating a solid dispersion with Polyvinyl pyrollidine (PVP-K30) and Guargum. Full Factorial designs are exploited to learn and research the effects of different variables on the quality determinant parameters. An appropriate statistical model was selected for the scrutiny of the enhanced dissolution pattern. Finally, these solid dispersions were incorporated into fast disintegrating tablets. Keywords: Lercanidipine Hydrochloride, Solid dispersion, Statistical design approach, Melt fusion method, Fast disintegrating tablet, In vivo studies

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

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.

Biopharmaceutical and Preclinical Studies of Zaleplon as Semisolid Dispersions with Self-emulsifying Lipid Surfactants for Oral Delivery

1970 ◽  
Vol 9 (1) ◽  
pp. 3102-3111
Author(s):  
Narendar Dudhipala ◽  
Arjun Narala ◽  
Dinesh Suram ◽  
Karthik Yadav Janga
Keyword(s):  
Oral Delivery ◽  
Molecular State ◽  
In Vivo Studies ◽  
In Vitro Dissolution ◽  
Content Uniformity ◽  
Phase Solubility ◽  
Microscopic Studies ◽  
Pure Drug

The objective of this present study is to develop a semisolid dispersion (SSD) of zaleplon with the aid of self-emulsifying lipid based amphiphilic carriers (TPGS E or Gelucire 44/14) addressing the poor solubility of this drug. A linear relationship between the solubility of drug with respect to increase in the concentration of lipid surfactant in aqueous medium resulting in AL type phase diagram was observed from phase solubility studies. Fusion method was employed to obtain semisolid dispersions (SSD) of zaleplon which showed high content uniformity of drug. The absence of chemical interactions between the pure drug, excipients and formulations were conferred by Fourier transmission infrared spectroscopic examinations. The photographic images from polarized optical microscopic studies revealed the change in crystalline form of drug to amorphous or molecular state. The superior dissolution parameters of zaleplon from SSD over pure crystalline drug interpreted from in vitro dissolution studies envisage the ability of these lipid surfactants as solubility enhancers. Further, the caliber of TPGS E or Gelucire 44/14 in encouraging the GI absorption of drug was evident with the higher human effective permeability coefficient and fraction oral dose of drug absorbed from SSD in situ intestinal permeation study. In conclusion, in vivo studies in Wister rats demonstrated an improvement in the oral bioavailability of zaleplon from SSD over control pure drug suspension suggesting the competence of Gelucire 44/14 and TPGS E as conscientious carriers to augment the dissolution rate limited bioavailability of this active

Spray Dried Formulation of 5-Fluorouracil Embedded with Probiotic Biomass: In Vitro and In Vivo Studies

2017 ◽  
Vol 9 (3) ◽  
pp. 310-322 ◽  
Author(s):  
Anshul Sharma ◽  
Malika Arora ◽  
Amit K. Goyal ◽  
Goutam Rath
Keyword(s):  
In Vivo Studies ◽  
Spray Dried ◽  
Probiotic Biomass

Preparation and optimization of controlled release nanoparticles containing cefixime using Central Composite design: An attempt to enrich its antimicrobial activity

2021 ◽  
Vol 18 ◽  
Author(s):  
Mohammad Ali Mahjoub ◽  
Pedram Ebrahimnejad ◽  
Fatemeh Shahlaee ◽  
Pouneh Ebrahimi ◽  
Zaynab Sadeghi-Ghadi
Keyword(s):  
Central Composite Design ◽  
Dissolution Rate ◽  
Ex Vivo ◽  
Chitosan Nanoparticles ◽  
Amorphous State ◽  
Scanning Tunneling ◽  
Release Kinetic ◽  
Calorimetric Analysis ◽  
Cell Culture Study ◽  
Central Composite

Background: Due to the increased resistance against existing antibiotics, research is essential to discover new and alternative ways to control infections induced by resistant pathogens. Objective: The goal of the current scrutinization was to enrich the dissolution rate and antibacterial property of cefixime (CEF) orally. Methods: To achieve the desired results, chitosan nanoparticles (NPs) containing CEF were fabricated using the ionic gelation method. Central Composite design has been applied to get the optimal formulation for the delivery of CEF. The effect of three variables such as the concentration of chitosan, tripolyphosphate, and tween 80 on the characteristics of NPs was evaluated. Results: The optimized NPs were a relatively monodispersed size distribution with an average diameter of 193 nm and a zeta potential of about 11 mV. The scanning tunneling microscope confirmed the size of NPs. The surface morphology of NPs was observed by scanning electron microscopy. The calorimetric analysis indicated the amorphous state of cefixime in the formulation. The dissolution rate of NPs in aqueous media was acceptable and the model of release kinetic for CEF from NPs followed the Peppas model. The potency of CEF in NPs against various types of bacteria was hopefully efficient. The ex- vivo release study demonstrated higher penetration of NPs from the rat intestine compared to free drug. The cell culture study showed the safety of the optimized formulation. Conclusion: It was concluded that CLN could be considered as a prospering system for the controlled delivery of CEF with advantaging its antibacterial effectiveness.

Optimization of Chronomodulated Delivery System Coated with a Blend of Ethyl Cellulose and Eudragit L100 by Central Composite Design: In Vitro and In Vivo Evaluation

2014 ◽  
Vol 9 (2) ◽  
pp. 95-105 ◽  
Author(s):  
Om Prakash Ranjan ◽  
Usha Y. Nayak ◽  
M. Sreenivasa Reddy ◽  
Swapnil J. Dengale ◽  
Prashant B. Musmade ◽  
...  
Keyword(s):  
Central Composite Design ◽  
Delivery System ◽  
Ethyl Cellulose ◽  
In Vivo Evaluation ◽  
Eudragit L100 ◽  
Central Composite

scholarly journals Fabrication of Carbamazepine Cocrystals: Characterization, In Vitro and Comparative In Vivo Evaluation

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Muhammad Wasim ◽  
Abdul Mannan ◽  
Muhammad Hassham Hassan Bin Asad ◽  
Muhammad Imran Amirzada ◽  
Muhammad Shafique ◽  
...  
Keyword(s):  
Physicochemical Properties ◽  
Oral Bioavailability ◽  
In Vivo Studies ◽  
Aliphatic Chain ◽  
Dissolution Profile ◽  
Maximum Solubility ◽  
In Vivo Evaluation ◽  
Hydrophobic Nature

Carbamazepine (CBZ) is an antiepileptic drug having low bioavailability due to its hydrophobic nature. In the current study, efforts are made to investigate the effect of dicarboxylic acid coformer spacer groups (aliphatic chain length) on physicochemical properties, relative humidity (RH) stability, and oral bioavailability of CBZ cocrystals. Slurry crystallization technique was employed for the preparation of CBZ cocrystals with the following coformers: adipic (AA), glutaric (GA), succinic (SA), and malonic acid (MA). Powder X-ray diffractometry and Fourier-transform infrared spectroscopy confirmed cocrystal preparation. Physicochemical properties, RH stability, and oral bioavailability of cocrystals were investigated. Among the prepared cocrystals, CBZ-GA showed maximum solubility as well as improved dissolution profile (CBZ-GA > CBZ-MA > CBZ-AA > pure CBZ > CBZ-SA) in ethanol. Maximum RH stability was shown by CBZ-AA, CBZ-SA, and CBZ-MA. In vivo studies confirmed boosted oral bioavailability of cocrystals compared to pure CBZ. Furthermore, in vivo studies depicted the oral bioavailability order of cocrystals as CBZ-GA > CBZ-MA > Tegral® > CBZ-AA > CBZ-SA > pure CBZ. Thus, pharmaceutical scientists can effectively employ cocrystallization technique for tuning physicochemical properties of hydrophobic drugs to achieve the desired oral bioavailability. Overall, results reflect no consistent effect of spacer group on physicochemical properties, RH stability, and oral bioavailability of cocrystals.

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