An analytical study of drug release kinetics from a degradable polymeric matrix

2018 ◽  
Vol 11 (01) ◽  
pp. 1850011 ◽  
Author(s):  
Koyel Chakravarty ◽  
D. C. Dalal

In modern days, biodegradable polymeric matrix used as the kingpin of local drug delivery system is in the center of attention. This work is concentrated on the formulation of mathematical model elucidating degradation of drug-loaded polymeric matrix followed by drug release to the adjacent biological tissues. Polymeric degradation is penciled with mass conservation equations. Drug release phenomenon is modeled by considering solubilization dynamics of drug particles, diffusion of the solubilized drug through polymeric matrix along with reversible dissociation/recrystallization process. In the tissue phase, reversible dissociation/association along with internalization processes of drug are taken into account. For this, a two-phase spatio-temporal model is postulated, which has ensued to a system of partial differential equations. They are solved analytically with appropriate choice of initial, interface and boundary conditions. In order to reflect the potency of the advocated model, the simulated results are analogized with corresponding experimental data and found laudable agreement so as to validate the applicability of the model considered. This model seems to foster the delicacy of the mantle enacted by important drug kinetic parameters such as diffusion coefficients, mass transfer coefficients, particle binding and internalization parameters, which is illustrated through local sensitivity analysis.

2019 ◽  
Vol 12 (04) ◽  
pp. 1950043
Author(s):  
Koyel Chakravarty ◽  
D. C. Dalal

In this paper, a mathematical model of drug release from polymeric matrix and consequent intracellular drug transport is proposed and analyzed. Modeling of drug release is done through solubilization dynamics of drug particles, diffusion of the solubilized drug through the polymeric matrix in addition to reversible dissociation/recrystallization process. The interaction between drug-receptor, drug-plasma proteins along with other intracellular endosomal events is modeled. This leads to a mixed system of partial and ordinary differential equations with associated pertinent set of initial and boundary conditions. Furthermore, besides the stability of the proposed model, several sub-models are also studied for their stability criteria. Prominence is provided to the reduced model system having requisite relevance to the original system where quasi steady state approximation (QSSA) theory is utilized. For the model to be potent enough to generate appropriate predictive results for drug delivery, the stability properties of equilibrium in the mathematical model are analyzed both analytically and numerically. Numerical simulation in the embodiment of graphical representations speaks about various vital characteristics of the underlying physical phenomena along with the importance and sensitized impact of the model parameters controlling significant biological functions. Probed new therapies and clinical procedures could be assessed considering the present mathematical model and its analysis as the basis framework in order to effectively enhance therapeutic efficacy and improved patient compliance. The present study confirms the necessity of stability analysis study so that advocated mathematical model can effectively complement the real physiological behavior of pharmacokinetics.


2021 ◽  
Vol 16 (1) ◽  
pp. 195-201
Author(s):  
Prerana Prakash ◽  
Pushpa Agrawal ◽  
AH Manjunatha Reddy

Immunotherapy has shown promising applications in cancer treatment as it boosts the systemic immune response. Existing immunotherapy strategies have certain drawbacks which can be addressed by engineered biomaterials. In this review, we focused on advanced immunotherapy methods involving implantable and injectable biomaterials for the treatment of cancer. Engineered biomaterials as carriers for immunomodulatory agents aid in the local drug delivery, thus reducing the frequency of off-target side effects. Also, biomaterial-based cancer vaccines have the potential to target specific tissues by finely altering the physical properties of the drug to achieve desired drug release kinetics.


2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Thomas Stahnke ◽  
Stefan Siewert ◽  
Thomas Reske ◽  
Wolfram Schmidt ◽  
Klaus-Peter Schmitz ◽  
...  

To prevent implant failure due to fibrosis is a major objective in glaucoma research. The present study investigated the antifibrotic effects of paclitaxel (PTX), caffeic acid phenethyl ester (CAPE), and pirfenidone (PFD) coated microstent test specimens in a rat model. Test specimens based on a biodegradable blend of poly(4-hydroxybutyrate) biopolymer and atactic poly(3-hydroxybutyrate) (at.P(3HB)) were manufactured, equipped with local drug delivery (LDD) coatings, and implanted in the subcutaneous white fat depot. Postoperatively, test specimens were explanted and analyzed for residual drug content. Fat depots including the test specimens were histologically analyzed. In vitro drug release studies revealed an initial burst for LDD devices. In vivo, slow drug release of PTX was found, whereas it already completed 1 week postoperatively for CAPE and PFD LDD devices. Histological examinations revealed a massive cell infiltration in the periphery of the test specimens. Compact fibrotic capsules around the LDD devices were detectable at 4–36 weeks and least pronounced around PFD-coated specimens. Capsules stained positive for extracellular matrix (ECM) components. The presented model offers possibilities to investigate release kinetics and the antifibrotic potential of drugs in vivo as well as the identification of more effective agents for a novel generation of drug-eluting glaucoma microstents.


Author(s):  
Rajesh Dubey ◽  
Udaya K. Chowdary ◽  
Venkateswarlu V.

A controlled release formulation of metoclopramide was developed using a combination of hypromellose (HPMC) and hydrogenated castor oil (HCO). Developed formulations released the drug over 20 hr with release kinetics following Higuchi model. Compared to HCO, HPMC showed significantly higher influence in controlling the drug release at initial as well as later phase. The difference in the influence can be explained by the different swelling and erosion behaviour of the polymers. Effect of the polymers on release was optimized using a face-centered central composite design to generate a predictable design space. Statistical analysis of the drug release at various levels indicated a linear effect of the polymers’ levels on the drug release. The release profile of formulations containing the polymer levels at extremes of their ranges in design space was found to be similar to the predicted release profile


2017 ◽  
Vol 23 (3) ◽  
pp. 467-480 ◽  
Author(s):  
Satyanarayan Pattnaik ◽  
Kamla Pathak

Background: Improvement of oral bioavailability through enhancement of dissolution for poorly soluble drugs has been a very promising approach. Recently, mesoporous silica based molecular sieves have demonstrated excellent properties to enhance the dissolution velocity of poorly water-soluble drugs. Description: Current research in this area is focused on investigating the factors influencing the drug release from these carriers, the kinetics of drug release and manufacturing approaches to scale-up production for commercial manufacture. Conclusion: This comprehensive review provides an overview of different methods adopted for synthesis of mesoporous materials, influence of processing factors on properties of these materials and drug loading methods. The drug release kinetics from mesoporous silica systems, the manufacturability and stability of these formulations are reviewed. Finally, the safety and biocompatibility issues related to these silica based materials are discussed.


Author(s):  
Anjali P.B ◽  
Jawahar N. ◽  
Jubie S. ◽  
Neetu Yadav ◽  
Selvaraj A. ◽  
...  

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.


Author(s):  
Sahil Kumar ◽  
Bandna Sharma ◽  
Tilak R. Bhardwaj ◽  
Rajesh K. Singh

Aims: In the present study, polymer-drug conjugates were synthesized based on azo-bond cleavage drug delivery approach for targeting erlotinib as anticancer drug specifically to the colon for the proficient treatment of colon cancer. Background: Colon cancer (CC) is the third commonly detected tumor worldwide and it make up about 10 % of all cases of cancers. Most of the chemotherapeutic drugs available for treating colon cancer are not only toxic to cancerous cells but also to the normal healthy cells. Among the various approaches to get rid of the adverse effects of anticancer agents, prodrugs are one of the most imperative approaches. Objective: The objective of the study is to chemically modify the erlotinib drug through azo-bond linkage and suitable spacer which will be finally linked to polymeric backbone to give desired polymer linked prodrug. The azo reductase enzyme present in colon is supposed to cleave the azo-bond specifically and augment the drug release at the colon. Methods: The synthesized conjugates were characterized by IR and 1H-NMR spectroscopy. The cleavage of aromatic azobond resulted in a potential colon-specific liberation of drug from conjugate studied in rat fecal contents. In vitro release profiles of polyphosphazene-linked conjugates of erlotinib have been studied at pH 1.2, pH 6.8 and pH 7.4. The stability study was designed to exhibit that free drug was released proficiently and unmodified from polyphosphazene-erlotinib conjugates having aromatic azo-bond in artificial colon conditions. Results: The synthesized conjugates were demonstrated to be stable in simulated upper gastro-intestinal tract conditions. The drug release kinetics shows that all the polymer-drug conjugates of erlotinib follow zero-order release kinetics which indicates that the drug release from the polymeric backbone is independent of its concentration. Kinetic study of conjugates with slope (n) shows the anomalous type of release with an exponent (n) > 0.89 indicating a super case II type of release. Conclusion: These studies indicate that polyphosphazene linked drug conjugates of erlotinib could be the promising candidates for the site-specific treatment of colon cancer with least detrimental side-effects.


Author(s):  
Kumar Nishchaya ◽  
Swatantra K.S. Kushwaha ◽  
Awani Kumar Rai

Background: Present malignant cancer medicines has the advancement of magnetic nanoparticles as delivery carriers to magnetically accumulate anticancer medication in malignant growth tissue. Aim: In the present investigation, a silica nanoparticles (MSNs) stacked with hydroxyurea were combined and was optimized for dependent and independent variables. Method: In this study, microporous silica nanoparticle stacked with neoplastic medication had been prepared through emulsification followed with solvent evaporation method. Prepared MSNs were optimized for dependent and independent variables. Different formulations were prepared with varying ratio of polymer, lipid and surfactant which affects drug release and kinetics of drug release pattern. The obtained MSNs were identified by FTIR, SEM, drug entrapment, in-vitro drug release, drug release kinetics study, stability testing in order to investigate the nanoparticle characteristics. Results: The percentage drug entrapment of the drug for the formulations F1, F2, F3, was found to be 27.78%, 65.52% and 48.26%. The average particle size for F2 formulation was found to be 520 nm through SEM. The cumulative drug release for the formulations F1, F2, F3 was found to be 64.17%, 71.82% and 32.68%. The formulations were found to be stable which gives controlled drug delivery for 6 hours. Conclusion: From the stability studies data it can be culminated that formulations are most stable when stored at lower temperature or in refrigerator i.e. 5˚C ± 3˚C. It can be concluded that MSN’s loaded with hydroxyurea is a promising approach towards the management of cancer due to its sustained release and less side effects.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1130
Author(s):  
Mariana Pires Figueiredo ◽  
Ana Borrego-Sánchez ◽  
Fátima García-Villén ◽  
Dalila Miele ◽  
Silvia Rossi ◽  
...  

This work presents the development of multifunctional therapeutic membranes based on a high-performance block copolymer scaffold formed by polyether (PE) and polyamide (PA) units (known as PEBA) and layered double hydroxide (LDH) biomaterials, with the aim to study their uses as wound dressings. Two LDH layer compositions were employed containing Mg2+ or Zn2+, Fe3+ and Al3+ cations, intercalated with chloride anions, abbreviated as Mg-Cl or Zn-Cl, or intercalated with naproxenate (NAP) anions, abbreviated as Mg-NAP or Zn-NAP. Membranes were structurally and physically characterized, and the in vitro drug release kinetics and cytotoxicity assessed. PEBA-loading NaNAP salt particles were also prepared for comparison. Intercalated NAP anions improved LDH–polymer interaction, resulting in membranes with greater mechanical performance compared to the polymer only or to the membranes containing the Cl-LDHs. Drug release (in saline solution) was sustained for at least 8 h for all samples and release kinetics could be modulated: a slower, an intermediate and a faster NAP release were observed from membranes containing Zn-NAP, NaNAP and Mg-NAP particles, respectively. In general, cell viability was higher in the presence of Mg-LDH and the membranes presented improved performance in comparison with the powdered samples. PEBA containing Mg-NAP sample stood out among all membranes in all the evaluated aspects, thus being considered a great candidate for application as multifunctional therapeutic dressings.


Polymers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 691
Author(s):  
O. Sánchez-Aguinagalde ◽  
Ainhoa Lejardi ◽  
Emilio Meaurio ◽  
Rebeca Hernández ◽  
Carmen Mijangos ◽  
...  

Chitosan (CS) and poly (vinyl alcohol) (PVA) hydrogels, a polymeric system that shows a broad potential in biomedical applications, were developed. Despite the advantages they present, their mechanical properties are insufficient to support the loads that appear on the body. Thus, it was proposed to reinforce these gels with inorganic glass particles (BG) in order to improve mechanical properties and bioactivity and to see how this reinforcement affects levofloxacin drug release kinetics. Scanning electron microscopy (SEM), X-ray diffraction (XRD), swelling tests, rheology and drug release studies characterized the resulting hydrogels. The experimental results verified the bioactivity of these gels, showed an improvement of the mechanical properties and proved that the added bioactive glass does affect the release kinetics.


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