Application of statistical design to evaluate critical process parameters and optimize formulation technique of polymeric nanoparticles

In advanced medication, drug-loaded polymeric nanoparticles (NPs) appeared as a novel drug delivery system with lots of advantages over conventional medicines. Despite all the advantages, NPs do not gain popularity for manufacturing hurdles. The study focused on the formulation difficulties and implementation of statistical design to establish an effective model for manufacturing NPs. In this study, physico-chemical properties of the drug and polymer (PLGA) were incorporated to understand the mechanistic insights of nanoformulations. Primarily, the process controlling parameters were screened by Plackett–Burman design and the critical process parameters (Cpp) were further fabricated by Box–Behnken design (BBD). The TLM-PLGA-NPs (telmisartan loaded PLGA NPs) exhibited particle size, encapsulation efficiency and zeta potential of 232.4 nm, 79.21% and −9.92 mV respectively. The NPs represented drug loading of 76.31%. Korsmeyer–Peppas model ( R 2 = 0.925) appeared to be the best fitted model for in vitro release kinetics of NPs. The model identified Fickian diffusion of TLM from the polymeric nanoparticles. The ANOVA results of variables indicate that BBD is a suitable model for the development of polymeric NPs. The study successfully identified and evaluated the correlation of significant parameters that were directly or indirectly influencing the formulations which deliberately produce desired nanoparticles with the help of statistical design.

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Fabrication and in vitro characterization of polymeric nanoparticles for Parkinson's therapy: a novel approach

Brazilian Journal of Pharmaceutical Sciences ◽

10.1590/s1984-82502014000400022 ◽

2014 ◽

Vol 50 (4) ◽

pp. 869-876 ◽

Cited By ~ 7

Author(s):

Neha Gulati ◽

Upendra Nagaich ◽

Shubhini Saraf

Keyword(s):

Drug Release ◽

Polymeric Nanoparticles ◽

Release Kinetics ◽

Mode Of Delivery ◽

Chitosan Nanoparticles ◽

Entrapment Efficiency ◽

Tween 80 ◽

Fickian Diffusion ◽

Novel Approach

The objective of the research was to formulate and evaluate selegiline hydrochloride loaded chitosan nanoparticles for the Parkinson's therapy in order to improve its therapeutic effect and reducing dosing frequency. Taguchi method of design of experiments (L9 orthogonal array) was used to get optimized formulation. The selegiline hydrochloride loaded chitosan nanoparticles (SHPs) were prepared by ionic gelation of chitosan with tripolyphosphate anions (TPP) and tween 80 as surfactant. The SHPs had a mean size of (303.39 ± 2.01) nm, a zeta potential of +32.50mV, and entrapment efficiency of SHPs was 86.200 ± 1.38%. The in vitro drug release of SHPs was evaluated in phosphate buffer saline (pH 5.5) using goat nasal mucosa and found to be 82.529% ± 1.308 up to 28 h. Release kinetics studies showed that the release of drug from nanoparticles was anomalous (non-fickian) diffusion indicating the drug release is controlled by more than one process i.e. superposition of both phenomenon, the diffusion controlled as well as swelling controlled release. SHPs showed good stability results as found during stability studies at different temperatures as mentioned in ICH guidelines. The results revealed that selegiline hydrochloride loaded chitosan nanoparticles are most suitable mode of delivery of drug for promising therapeutic action.

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Freeze drying optimization of polymeric nanoparticles for ocular flurbiprofen delivery: effect of protectant agents and critical process parameters on long-term stability

Drug Development and Industrial Pharmacy ◽

10.1080/03639045.2016.1275669 ◽

2017 ◽

Vol 43 (4) ◽

pp. 637-651 ◽

Cited By ~ 10

Author(s):

Gladys Rosario Ramos Yacasi ◽

Ana Cristina Calpena Campmany ◽

María Antonia Egea Gras ◽

Marta Espina García ◽

María Luisa García López

Keyword(s):

Process Parameters ◽

Freeze Drying ◽

Polymeric Nanoparticles ◽

Term Stability ◽

Long Term Stability ◽

Critical Process Parameters ◽

Critical Process

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Design and Synthesis of a Novel Gabapentin-Phosphotidylcholine Conjugate for Targeting to Phospholipase A2 Enzyme through Nanostructured Lipid Carrier

Current Computer - Aided Drug Design ◽

10.2174/1573409916666201224153414 ◽

2020 ◽

Vol 16 ◽

Author(s):

Anjali P.B ◽

Jawahar N. ◽

Jubie S. ◽

Neetu Yadav ◽

Selvaraj A. ◽

...

Keyword(s):

Drug Release ◽

Phospholipase A2 ◽

Release Kinetics ◽

Entrapment Efficiency ◽

Structural Analog ◽

Fickian Diffusion ◽

Release Kinetic ◽

Nanostructured Lipid Carrier ◽

Discovery Studio

Background: : Epilepsy is a genuine neurological turmoil that effects around 50 million individuals around the world. Practically 30% of epileptic patients experience the ill effects of pharmaco-obstruction, which is related with social seclusion, subordinate conduct, low marriage rates, joblessness, mental issues and diminished personal satisfaction. At present accessible antiepileptic drugs have a restricted viability, and their negative properties limit their utilization and cause challenges in patient administration. Gabapentin 1-(aminomethyl)cyclohexane acetic acid, Gbp , (trade name Neurontin), a structural analog of γ-aminobutyric acid (GABA), BCS class 3 drug with having permeability issues. Objective: This work was an attempt to formulate and characterize a new approach to treat epilepsy by targeting to Phospholipase A2 Enzyme through Nanostructured Lipid Carrier. Methods: Docking studied carried out using Accelrys Discovery studio 4.1 Client and gabapentin and phosphotidylcholine were conjugated through chemical conjugation. Nanostructured lipid carrier (NLC) was prepared using hot homogenization technique. Results: The libdock score of Gabapentin- Phosphotidylcholine conjugate (192.535) were found to be more than Gabapentin (77.1084) and Phosphotidylcholine (150.212). For the optimized formulation the particle size (50.08), zeta potential (-1.48), PDI (0.472) and entrapment efficiency (77.8) was observed. The NLC was studies for in-vitro drug release studies and release kinetics. Finally found that the drug release from the NLC followed Higuchi release kinetic and the mode of drug release from the NLC was found to be Non- Fickian diffusion. Conclusion: The formulated Nanostructured lipid carrier of Gabapentin-Phosphotidylcholine conjugate may be able to use to prevent seizure.

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Designing ultra-small nanostructured lipid carriers: critical process parameters

10.3390/iecp2020-08691 ◽

2020 ◽

Author(s):

Maria Mendes ◽

João Basso ◽

João Sousa ◽

Alberto Pais ◽

Carla Vitorino

Keyword(s):

Process Parameters ◽

Nanostructured Lipid Carriers ◽

Critical Process Parameters ◽

Critical Process

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Determining Critical Process Parameters and Process Robustness in Preparative Chromatography - A Model-Based Approach

Chemical Engineering & Technology ◽

10.1002/ceat.200900019 ◽

2009 ◽

Vol 32 (6) ◽

pp. 903-911 ◽

Cited By ~ 26

Author(s):

M. Degerman ◽

K. Westerberg ◽

B. Nilsson

Keyword(s):

Process Parameters ◽

Preparative Chromatography ◽

Process Robustness ◽

Model Based ◽

Critical Process Parameters ◽

Critical Process

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Formulation and investigation of crushed puffed rice-chitosan-HPMC based polymeric blends as carrier for sustained stomach specific drug delivery of piroxicam using 3(2) Taguchi mathematical design studies

International Current Pharmaceutical Journal ◽

10.3329/icpj.v6i11.36435 ◽

2018 ◽

Vol 6 (11) ◽

pp. 61-80 ◽

Cited By ~ 1

Author(s):

Shashank Soni ◽

Veerma Ram ◽

Anurag Verma

Keyword(s):

Drug Release ◽

Release Kinetics ◽

Drug Loading ◽

Hydroxypropyl Methylcellulose ◽

Research Work ◽

Pharmaceutical Journal ◽

Weight Variation ◽

Zero Order Release ◽

Puffed Rice

In the present experimental investigation an attempt has been made to assess the utility of Crushed Puffed Rice (CPR)-High Molecular Weight Chitosan (HMWCH)-Hydroxypropyl Methylcellulose K15M (HPMC K15M) as a polymeric carrier for the sustained stomach delivery of Piroxicam (PRX). A total of nine formulations were prepared by using 3 (2) Taguchi factorial design, physically blending drug and polymer(s) followed by encapsulation into hard gelatin capsules size 1. The prepared capsules were evaluated for various performance such as weight variation, drug contents, in vitro buoyancy and drug release in 0.1 M HCl. The effect of drug loading on in vitro performance of the formulations was also determined. Crushed puffed rice (CPR) remained buoyant for up to average time span of 06 hr as an unwetted irregular mass in 0.1 M HCl. However, when combined with HMWCH or HPMC K15M or HPMC K15M + HMWCH a low -density cylindrical raft type hydrogel was formed which remained buoyant for up to 12 hr and released up to 99% drug in a sustained manner from 8 to 12 hr following zero order release kinetics. It was also observed that drug release from drug + CPR matrices followed Fickian mechanism. Combination of CPR + HMWCH or HMWCH + HPMC K15M also follows Fickian mechanism. Obtained data from the research work suggests that CPR in combination with HMWCH or HPMC K15M or HPMC has sufficient potential to be used as a carrier for stomach specific delivery of gastric irritant drug like PRX.Soni et al., International Current Pharmaceutical Journal, April 2018, 6(11): 61-80http://www.icpjonline.com/documents/Vol6Issue11/01.pdf

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Application of Statistical Design to Assess the Critical Process Parameters of Ethanol Injection Method for the Preparation of Liposomes

Dhaka University Journal of Pharmaceutical Sciences ◽

10.3329/dujps.v18i1.41897 ◽

2019 ◽

Vol 18 (1) ◽

pp. 103-111 ◽

Cited By ~ 1

Author(s):

Sayani Bhattacharyya ◽

Bharani S Sogali

Keyword(s):

Particle Size ◽

Process Parameters ◽

Particle Size Analysis ◽

Polydispersity Index ◽

Size Analysis ◽

Ethanol Injection ◽

Injection Method ◽

Critical Process Parameters ◽

Critical Process ◽

Ethanol Injection Method

In the present study custom screening design was employed to observe the effect of four critical process parameters on particle size and polydispersity index of the liposomal formulation made by ethanol injection method. The four process parameters selected were lipid ratio, rate of injection, phase volume ratio and rotational speed of magnetic stirring. Eight different liposomal formulations were prepared using the design. The formulations were subjected to particle size analysis. The analysis was done at a significance level p<0.05 and found that the process parameters had significant effect on the particle size and polydispersity index of the formulations. The design was optimized for the individual responses with an overall desirability of more than 50%. Three batches of liposomes were formulated at optimized process parameters which matched the target as predicted by the design. Therefore, it can be concluded that the design was effective in production of nano sized stable monodisperse liposomes by ethanol injection method. Dhaka Univ. J. Pharm. Sci. 18(1): 103-111, 2019 (June)

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FORMULATION AND EVALUATION OF MUCOADHESIVE MICROSPHERES OF AN ANTI-MIGRAINE DRUG

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v8i5.1943 ◽

2018 ◽

Vol 8 (5) ◽

pp. 465-474

Author(s):

S PADMA PRIYA ◽

AN Rajalakshmi ◽

P Ilaveni

Keyword(s):

Drug Release ◽

Sustained Release ◽

Sodium Alginate ◽

Release Kinetics ◽

Drug Loading ◽

Research Work ◽

Entrapment Efficiency ◽

Polyvinyl Pyrrolidone ◽

Anti Migraine Drug

Objective: The objective of this research work is to develop and evaluate mucoadhesive microspheres of an anti-migraine drug for sustained release. Materials and Methods: Mucoadhesive microspheres were prepared by emulsification method using Sodium alginate (SA), polyvinyl pyrrolidone (PVP) and Chitosan in the various drug-polymer ratios of 1:1, 1:2 and 1:3. Nine formulations were formulated and evaluated for possible drug polymer interactions, percentage yield, micromeritic properties, particle size, drug content, drug entrapment efficiency, drug loading, swelling index, In-vitro wash off test, in vitro drug release, surface morphology and release kinetics. Results: The results showed that no significant drug polymer interaction in FTIR studies. Among all the formulations SF3 containing sodium alginate showed 77.18% drug release in 6hrs. Conclusion: Amongst the developed mucoadhesive microspheres, SF3 formulation containing sodium alginate exhibited slow and sustained release in a controlled manner and it is a promising formulation for sustained release of Sumatriptan succinate. Keywords: Mucoadhesive microspheres, Sodium alginate, polyvinyl pyrrolidone, Chitosan, sustained release.

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Design and Characterization of Combinational Domperidone-Famotidine Floating Drug Delivery System - In vitro and In vivo studies

Ars Pharmaceutica (Internet) ◽

10.30827/ars.v62i2.15810 ◽

2021 ◽

Vol 62 (2) ◽

pp. 144-162

Author(s):

Mounika Chidurala ◽

Raveendra Reddy J

Keyword(s):

Drug Release ◽

Oral Administration ◽

Quality By Design ◽

Release Kinetics ◽

Cost Effective ◽

Fickian Diffusion ◽

In Vivo Studies ◽

Pharmacokinetic Studies

Introduction: The drawbacks assosiated with oral administration of drugscan be controlled or minimized by gastro retentive formulations that remain buoyant within the stomach for an extended time by providing prolonged gastric retention and releasethe drug in an exceedingly extended manner thereby improving bioavailability. The current research was to develop and optimize Domperidone and Famotidine floating tablets with extended release by Quality by Design approach. Method: Based on QTPP (Quality Target Product Profile), CQAs (Critical Quality Attributes)wereidentified. Risk analysis by the evaluation of formulation and process parameters showed that optimizing the levels of polymers could reduce high risk to achieve the target profile. A 23factor experimental design with midpoints was selected for statistical analysis and optimization. Results: HPMC K100 and Carbopol 934P had a positive effect while ethyl cellulose demonstrated a negative effect on the selected responses. Drug release kinetics followed the first-order release with Higuchi diffusion and Fickian diffusion. Optimized formula satisfying all the required parameters was selected and evaluated. The predicted response values were in close agreement with experimental response values. Abdominal X-ray imaging after oral administration of the tablets on a healthy rabbit’s stomach confirmed the extended floating behavior with shorter lag time. In vivo, pharmacokinetic studies in rabbits revealed that the optimized formulation exhibited prolonged drug release with enhanced Cmax, tmax, AUCo-t, and t1/2 of an optimized product when compared to the marketed product. Conclusions: It has been concluded that the application of Quality by Design in the formulation and optimization reduced the number of trials to produce a cost-effective formula.

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