A Smart Approach for Delivery of Nanosized Phenytoin using Biomaterial Isolated from Fragaria ananassa

The purpose of this research was to isolate the smart biopolymer from the fruit pulp of Fragaria × ananassa (garden strawberry). We isolated natural fruit pulp to evaluate the potentiality of biopolymer in delivery of nanosized lamotrigine as an antiepileptic drug. Lamotrigine was nanosized by screening its nano-size particle by UV method. The nanosized lamotrigine was used for preparation of bionanoparticles (LF1-LF8) by sonication method. The isolated biopolymer was characterized for DSC, FTIR, NMR, Mass and Zeta particle size analysis. The obtained results confirm its polymeric nature in different analysis. The prepared bionanoparticles showed the release of lamotrigine in sustained manner over 36 hours. The release kinetic study was done by using the BIT-SOFT 1.12 software and T50% and T80%, r2 were calculated. All the formulation showed more than 99.78% drug release. The In-vitro release study of different formulations showed the % drug release from 90.92% to 99.78%. The different formulations were evaluated for the In-vitro release study and release kinetic was studied. The formulation LF5 was found to be the best formulation having T50% of 17 hours and T80% of 29 hours with r2 value of 0.9925. The best formulation LF5 showed up to 90.925% drug release over 36 hours. According to the release kinetic study, the best-fit model was found to be Koresmayer-Peppas and the mechanism of drug release was found to be anomalous transport. The results obtained from different evaluations like percentage entrapment efficiency, particle size, release study, kinetic studies and stability study revealed that isolated biopolymer has good potentiality to form bionanoparticles and it can be safely used as an alternative to synthetic and semisynthetic polymers for the preparation of lamotrigine loaded stable bionanoparticles

The research aims to develop bionanosuspension using a biopolymer isolated from Fragaria ananassa fruit that constitutes potential and natural polymeric properties. At first, the biomaterial was isolated from the natural fruit pulp of Fragaria ananassa by an economical method of isolation. The model drug was nanosized by a novel sonication method. The isolated biopolymer was characterized for its polymeric properties, and its potential capabilities were evaluated in the delivery of nanosized phenytoin. The isolated biopolymer was characterized for DSC, FTIR, NMR, mass, and scanning electron microscopy. The isolated biomaterial was used for the preparation of phenytoin-loaded bionanosuspension with other excipients. The bionanoparticles were also characterized by different analytical testing such as FTIR, DSC, and SEM to confirm any interaction between model drug and biopolymer.The prepared bionanoparticles showed the release of phenytoin in a sustained manner over 36 hours. The release kinetic study was done using the BIT-SOFT 1.12 software and other parameters such as t50%, t80%, and r2 were calculated. The formulation PFr6 was considered best having t50% in 18.22 hours and t80% in 29.62 h with an r2 value of 0.9793. This formulation showed up to 87.89% drug release within 36 hours. The prepared bio-nanosuspension was found to be stable and in a well-dispersed state. The dried bionanosuspension evaluation revealed no interaction between model drug and biopolymer without any loss of characteristic peaks. Therefore, the isolated biopolymer can be safely used to prepare stable bionanosuspension loaded with nanosized phenytoin.

Polymers influencing transportability profile of drug

Insights into the swelling process and drug release mechanisms from cross-linked pectin/high amylose starch matrices

Hydrogel nanoparticles have gained attention in recent years as they demonstrate the features and characters of hydrogels and nanoparticles at the same time. In the present study chitosan and carrageenan have been used, as hydrogel nanoparticles of mercaptopurine are developed using natural, biodegradable, and biocompatible polymers like chitosan and carrageenan. As these polymers are hydrophilic in nature, the particles will have a long life span in systemic circulation. Hydrogel nanoparticles with mercaptopurine is form an antileukemia drug by the counter polymer gelation method. Fourier-Transform Infrared (FT-IR) studies have shown a compatibility of polymers with the drug. The diameter of hydrogel nanoparticles was about 370 – 800 nm with a positive zeta potential of 26 – 30 mV. The hydrogel nanoparticles were almost spherical in shape, as revealed by scanning electron microscopy (SEM). Drug loading varied from 9 to 17%. Mercaptopurine released from the nanoparticles at the end of the twenty-fourth hour was about 69.48 – 76.52% at pH 7.4. The drug release from the formulation was following zero order kinetics, which was evident from the release kinetic studies and the mechanism of drug release was anomalous diffusion, which indicated that the drug release was controlled by more than one process.

The main purpose of this work was to develop biomedical electrospun nanofibrous mats based on a poly(vinyl alcohol)/poly(ɛ-caprolactone) (80/20) hybrid with a defined drug release rate using tetracycline hydrochloride as a model drug. The electrospinning process parameters, such as polymer solution concentration, distance between injecting syringe tip/collector, voltage, injected flow rate and the polyvinyl alcohol cross-linking time were optimized via a D-optimal design method for a suitable nanofiber diameter with an optimal drug release rate. The morphology of nanofibers and their mean diameters were studied by a scanning electron microscopy technique. The results showed that the mean diameters of nanofibers were significantly reduced after drug loading. The swelling, weight loss and biodegradability of nanofibers samples investigated by FTIR were also determined. Two main mechanisms via penetration and erosion were evaluated. In vitro drug release in a phosphate buffer environment at pH=7.2 for the samples demonstrated that the polymer type and hydrophilic nature of the polymer/drug system is very effective in the kinetics and mechanism of drug release. Hybridization of poly(vinyl alcohol)/poly(ɛ-caprolactone) with a known ratio showed to be a suitable and useful method in the electrospinning of nanofibers samples for superior control of the drug release rate. Finally, nanofibrous mats of polyvinyl alcohol and polyvinyl alcohol/poly(ɛ-caprolactone) hybrid (80/20) had much better drug release rate characteristics for tetracycline hydrochloride as a model drug compared with cast film samples loaded with the same drug. Open image in new window

Objective: The nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medications in the world because of their demonstrated efficacy in reducing pain and inflammation. The arthritis, pain and inflammation are effectively treated with Lornoxicam, an effective NSAIDs. Because the drug is weakly acidic, it is absorbed easily in the GI tract, and has a short biological half-life of 3 to 5 hours. To meet the objectives of this investigation, we developed a modified release dosage form to provide the delivery of lornoxicam at sustained rate which was designed to prolong its efficacy, reduce dosage frequency, and enhance patient compliance. The present research work was focused on the development of lornoxicam microspheres using natural polymer like okra gum extracted from the pods of Abelmoschus esculentus Linn. and synthetic polymer like ethyl cellulose along with sodium alginate prepared by Ca2+ induced ionic-gelation cross-linking in a complete aqueous environment were successfully formulated.
 Materials and Method: The microspheres were prepared by using sodium alginate with natural polymer (okra gum) and synthetic polymer (ethyl cellulose) in different ratios by Ca2+ induced ionic-gelation cross-linking. The formulations were optimized on the basis of drug release up to 12 hrs. The physicochemical characteristics of Lornoxicam microspheres such as drug polymer interaction study by Fourier Transform Infrared (FTIR) and further confirmation by Differential Scanning Calorimetry (DSC) and X-ray Diffraction (XRD). The formulated microspheres were characterized for particle size, percentage drug entrapment efficiency, micromeritic properties, surface morphology, percentage swelling index, in-vitro drug release study and mechanism of drug release.
 Results and Discussion: The FTIR Spectra revealed that there was no interaction between polymer and Lornoxicam which was further confirmed by DSC and XRD. All the formulated Lornoxicam microspheres were spherical in shape confirmed by SEM. The microspheres exhibited good flow properties and also showed high percentage drug entrapment efficiency. All the batches have excellent flow properties with angle of repose in the range of 25.38° ± 0.04 to 30.41° ± 0.07, carr’s index and hausner’s ratios in the range of 10.40% ± 0.018 to 16.66% ± 0.012 and 1.128 ± 0.09 to 2.225 ± 0.01, respectively. The optical microscopic studies revealed that the mean particle size of all the formulations were found in the range of 819.46 ± 0.07 to 959.88 ± 0.02 μm and percentage of drug entrapment were found to be between 72.35 ± 0.02 to 90.00 ± 0.05. Swelling index of prepared microspheres revealed that with increasing the polymer ratios, there were increase in the swelling of prepared microspheres, showing in the range of 600.76 ± 0.42 to 690.11 ± 0.03% for okra gum microspheres at the end of 9 hr in comparison with ethyl cellulose microspheres which ranges between 179.71 ± 0.07 to 227.73 ± 0.05% at the end of 7 hr. In-vitro drug release of prepared microspheres formulation code LSO4 and LSE4 were found to be 88.654 ± 0.25% and 93.971 ± 0.20% respectively at the end of 12 hr. It was suggested that increase in polymer concentration, the drug release from the prepared microspheres got retarded producing sustained release of lornoxicam. In-vitro drug release data obtained were fitted to various release kinetic models to access the suitable mechanism of drug release. Drug release from lornoxicam-loaded alginate-okra gum microspheres followed a pattern that resembled sustained release (Korsemeyer-Peppas model) (R2 = 0.9925 to 0.9951), and n ≤ 1 indicated anomalous diffusion (non-Fickian), supercase-II transport mechanism LSO4 (n = 1.039) over a period of 12 hour underlying in-vitro drug release. Moreover, zero order model (R2 = 0.9720 to 0.9949) were found closer to the best-fit Korsemeyer - Peppas model.
 In addition, the drug release from lornoxicam-loaded alginate-ethyl cellulose microspheres also follow Korsemeyer-Peppas model (R2 = 0.9741 to 0.9973) with near to Hixson-Crowell model (R2 = 0.9953 to 0.9985) and n < 1 indicated non-Fickian diffusion or anomalous transport mechanism. Moreover, first order model with non-Fickian diffusion mechanism (R2 = 0.9788 to 0.9918) were found closer to the best-fit Korsemeyer-Peppas model/ Hixson-Crowell model.
 Conclusion: The present study conclusively demonstrates the feasibility of effectively encapsulating Lornoxicam into natural polymer (okra gum) and synthetic polymer (ethyl cellulose) to form potential sustained drug delivery system. In conclusion, drug release over a period of 12 hrs, could be achieved from these prepared microspheres. A pH-dependent swelling and degradation of the optimized microspheres were also observed, which indicates that these microspheres could potentially be used for intestinal drug delivery.

This study was carried out to investigate the effect of chemical preservatives on strawberry juice. The samples were; pasteurized strawberry juice (T0), pasteurized strawberry juice with 20% sucrose (T1), pasteurized juice with 0.1% sodium benzoate (T0), pasteurized juice with 20% sucrose and 0.1% sodium benzoate (T3), pasteurized juice with 0.1% potassium sorbate (T4) pasteurized juice with 2% sucrose and 0.1% potassium sorbate (T5) pasteurized juice with 0.05% sodium benzoate and 0.05% potassium sorbate (T6) pasteurized juice with 20% sucrose, 0.05% sodium benzoate and 0.05% potassium sorbate (T7) pasteurized juice with 0.1% sodium benzoate and 0.1% potassium sorbate (T8) and pasteurized juice with 20% sucrose, 0.1% potassium sorbate and 0.1% sodium benzoate (T9). The samples were stored at 4 - 15°C for three months. T0and T1 were rejected soon due to spoilage. Minimum ascorbic acid content was reduced in T9 (9.8%), while maximum in T2 (26%). Acidity increased from 1.39 to 2.38% with maximum in T1 and T9. pH decreased from 3.29 to 2.22. Reducing sucrose increased from 15.7 to 17.8 and non-reducing sucrose decreased from 11.6 to 8.3. The total soluble solids (TSS) increased from 16.5 to 17.4° brix with maximum in T0 (60%) and minimum in T6 (5.6). Treatments T9, T7 T5 and T3 were found most acceptable in maintaining the sensory characteristics compared to others during storage. Minimum microbial load were observed in T9 and maximum in T0 and T1 (uncountable). Among all the treatments T9 were most effective in maintaining the sensory and nutritional quality during storage. Key words: Strawberry juice, pasteurization, benzoate, benzoate, citric acid, sucrose.

In this study, polyurethane‐films loaded with diclofenac were used to analyze the drug release kinetics and mechanisms. For this purpose, the experimental procedures were developed under static and dynamic conditions with different initial drug loads of 10, 20, and 30%. In the dynamic condition, to better simulate the biological flow, drug release measurements were investigated at flow rates of 7.5 and 23.5 ml/s. These values indicate the flow rate of the internal carotid artery (ICA) for a normal state of a body and for a person during the exercise, respectively. The experimental data were analyzed and adjusted by Higuchi, Korsmeyer–Peppas, First‐order, zero‐order, and Peppas–Sahlin models in order to understand the mechanisms contributed. Finally, drug release mechanisms were specified by investigating the model correlation coefficients. Experimental results showed that increasing the flow rate and initial drug loads enhance drug liberation. In addition, the rate of release is more influenced by the drug dosage in the static state. The analysis revealed that diffusion, burst, and osmotic pressure are the principal mechanisms contributed. Moreover, Fickian type was the dominant mechanism at all duration of release. However, it was discovered using Peppas–Sahlin model that the contribution of the diffusion mechanism decreases with increasing flow rate and initial dosage. Furthermore, the tests at different drug dosages showed that the number of stages in medication release profile is independent of the flow rate and the medicine percentage. One can conclude that the drug release kinetic in static state is more influenced by drug dosage compared with dynamic state.

Matrix technologies have often proven popular among the oral controlled drug delivery technologies because of their simplicity, ease in manufacturing, high level of reproducibility, stability of the raw materials and dosage form, and ease of scale-up and process validation. Technological advancements in the area of matrix formulation have made controlled-release product development much easier than before, and improved upon the feasibility of delivering a wide variety of drugs with different physicochemical and biopharmaceutical properties. This is reflected by the large number of patents filed each year and by the commercial success of a number of novel drug delivery systems based on matrix technologies.Matrix-based delivery technologies have steadily matured from delivering drugs by first-order or square-root-of-time release kinetics to much more complex and customized release patterns. In order to achieve linear or zero-order release, various strategies that seek to manipulate tablet geometry, polymer variables, and formulation aspects have been applied. Various drug, polymer, and formulation-related factors, which influence the in situ formation of a polymeric gel layer/drug depletion zone and its characteristics as a function of time, determine the drug release from matrix systems.Various mathematical models, ranging from simple empirical or semi-empirical (Higuchi equation, Power law) to more complex mechanistic theories that consider diffusion, swelling, and dissolution processes simultaneously, have been developed to describe the mass transport processes involved in matrix-based drug release. Careful selection of an appropriate model for drug release provides insight to the underlying mass transport mechanisms and helps in predicting the effect of the device design parameters on the resulting drug-release rate. Thus, a basic understanding of release kinetics and appropriate mechanisms of drug release from matrix system and their inter-relationships may minimize the number of trials in final optimization, thereby improving formulation development processes.

Background: Hydrophilic matrix formulations are important and simple technologies that are used to manufacture sustained release dosage forms. Method: Hydroxypropyl methylcellulose-based matrix tablets, with and without additives, were manufactured to investigate the rate of hydration, rate of erosion, and rate and mechanism of drug release. Scanning electron microscopy was used to assess changes in the microstructure of the tablets during drug release testing and whether these changes could be related to the rate of drug release from the formulations. Results: The results revealed that the rate of hydration and erosion was dependent on the polymer combination(s) used, which in turn affected the rate and mechanism of drug release from these formulations. It was also apparent that changes in the microstructure of matrix tablets could be related to the different rates of drug release that were observed from the test formulations. Conclusion: The use of scanning electron microscopy provides useful information to further understand drug release mechanisms from matrix tablets.

The purpose of the present study was to formulate and evaluatesustained release tablet of Torsemide. Sustained release tablets of Torsemide were formulated with different concentrations of HPMC K4M and HPMC K100M by using wet granulation technique and evaluated for the different evaluation parameters such as thickness, hardness, drug content uniformity, friability, in-vitro drug releasestudies, release kinetic studies and stability studies were performed. All the evaluation parameters results were significant. In-vitro drug releasestudies were performed and drug release kinetics evaluated using the linear regression method was found to follow Zero order, First order, Matrix and Korsemeyer and Peppas’ equation. The drug release mechanism was found Fickian type in most of theformulations. The prepared formulation shows better and significant results for all the evaluated parameters. The formulation F9 shows maximum percentage of drug release (98.2 %) and prolonged release fortime period of about 12 h, thereby improves the bioavailability and patient compliance.

Objective: Development and evaluation of selegiline-loaded bio-nanosuspensions using biopolymer which was isolated from seeds of Buchanania lanzan (Chironji), used as biostabilizer and compared with standard polymer.
 Methods: The selegiline-loaded bio-nanosuspensions were prepared using novel biopolymer and standard stabilizer (hydroxypropyl methylcellulose) by sonication solvent evaporation method with different ratios (1%, 2%, 3%, 4%, and 5%) and evaluated for particle size, polydispersity index, zeta potential, pH stability studies, percentage entrapment efficacy, in vitro drug release, and stability studies.
 Results: The prepared selegiline bio-nanosuspensions were subjected to the best formulation based on comparison of above-mentioned evaluation parameters, so Fb2 (2%) formulation was found to be the best formulation showing an R2=0.9842, T50% of 32 h and T80% of 70 h, respectively. According to the release kinetics, the best fit model was found to be Peppas-Korsmeyer with Fickian diffusion (Higuchi matrix) as the mechanism of drug release, and Fs5 (5%) formulation was found to be the best formulation showing an R2=0.9564, T50% of 25 h and T80% of 60 h, respectively. According to the release kinetics, the best fit model was found to be Peppas-Korsmeyer with Fickian diffusion (Higuchi matrix) as the mechanism of drug release. The biopolymer provided excellent stability for the formulation and resulting particle size for the best formulation was found to be 360 nm. The best formulation was found to be polydispersity index of 0.43 with zeta potential of −5.12 mV.
 Conclusion: The prepared bio-nanosuspensions using biopolymer were found to be safe and compatible with the novel drug delivery for the treatment of depression in comparison of standard polymer.

Tablets used for extended drug release commonly contain large amounts of drugs. The corresponding drug release mechanism thus has to be well-known and invariable under numerous conditions in order to prevent any uncontrolled drug release. Particularly important is the stability and invariability of the release mechanism in the presence of alcohol due to the possible occurrence of the dose dumping effect. The effect of 3D printing (3DP) coating on the drug release mechanism and the drug release rate was studied as a possible tool for the prevention of the alcohol-induced dose dumping effect. Three types of matrix tablets (hydrophilic, lipophilic, and hydrophilic-lipophilic) were prepared by the direct compression method and coated using 3DP. The commercial filament of polyvinyl alcohol (PVA) and the filament prepared from hypromellose by hot melt extrusion (HME) were used as coating materials. Both coating materials were characterized by SEM, DSC, Raman spectroscopy, and PXRD during particular stages of the processing/coating procedure. The dissolution behavior of the uncoated and coated tablets was studied in the strongly acidic (pH 1.2) and alcoholic (40% of ethanol) dissolution media. The dissolution tests in the alcoholic medium showed that the Affinisol coating was effective in preventing the dose dumping incidence. The dissolution tests in the acidic dissolution media showed that the Affinisol coating can also be useful for the delayed release of active substances.

Purpose: To investigate the characteristics of sustained drug release systems established by an arginine-glycine-aspartic acid (RGD) peptide hydrogel and mitomycin C (MMC) in vitro, and verify their antiscar effects in rat ocular injury model. Methods: Low, medium, and high loading doses of MMC were added to 5 mL 0.25%, 0.5%, and 1% wt RGD peptide hydrogel, respectively, to prepare 9 ratios of MMC-RGD systems. Drug release characteristics of the systems in phosphate-buffered saline solution were investigated by plotting the drug release curves and fitting them with mathematical models in OriginPro8.0 software. Appropriate ratios of MMC-RGD systems were selected as treatment in rat ocular injury model. Scar formation was observed by Masson staining and immunohistochemical staining with alpha-smooth muscle actin (α-SMA) and fibronectin (FN). Results: Nine ratios of MMC-RGD systems could release drug slowly. The maximum drug release proportions of all systems were >80%, and the time to maximum release proportions statistically prolonged with the increase of drug loading. Fitting with mathematical models indicated that the mechanisms of drug release were mainly Fick diffusion at early stage and Anomalous Transport at later stage. Systems of 1% wt RGD hydrogel were evaluated in animal experiments, which could inhibit hyperplasia of collagen and expression of α-SMA and FN. Conclusions: The RGD peptide hydrogel could be used as the carrier of MMC to establish sustained drug release system, which could inhibit scar formation after rat's ocular injury.