Zero-order Release Profile Research Articles

Design, Optimization, and Evaluation of Chitosan-2-mercaptobenzoic Acid as a Dual-functionalized Thiomer

Aims: This study aimed to develop and evaluate mucoadhesive microspheres for the controlled release of zidovudine using a novel dual-functionalized polymer. Background: Mucoadhesive polymers have recently been widely used to prolong the GI residence time and to modulate the release impact of various mucoadhesive dosage forms. In the present study, a recently synthesized chitosan derivative, chitosan-2-mercapto benzoic acid, was used as a mucoadhesive polymer, which was further developed as a dosage form for improving oral bioavailability of zidovudine drug. Objective: The objective of this study is to evaluate the impact of a novel thiolated derivative, chitosan-2-mercaptobenzoic acid, on the oral bioavailability of the drug zidovudine. Methods: The microspheres were prepared using an emulsification crosslinking method with TPP as the crosslinking agent. Techniques such as FTIR, and DSC were employed to analyze the microspheres, along with drug content, entrapment efficiency, dissolution studies, mucoadhesion, ex vivo permeation, and in vivo evaluations. Results: Results from FTIR spectroscopy and DSC analysis revealed no interaction between the drug and polymers. The release kinetics and characterization assessments indicated a zero-order release profile with anomalous and super case-II transport types. Ex vivo permeation studies on goat intestinal mucosa demonstrated enhanced mucoadhesive properties and permeability with the optimized microspheres fabricated using thiomers compared to conventional oral therapy. Pharmacokinetic investigations showed higher zidovudine plasma levels and Cmax with the administration of microspheres, particularly those composed of thiomers. The AUC0-24h values for thiomer microspheres were significantly greater than controls and chitosan microspheres, indicating improved oral bioavailability potential. Conclusion: In conclusion, zidovudine-loaded thiomer-based mucoadhesive microspheres showed promising results with the ability to enhance the drug's oral bioavailability.

Design, Optimization and In vitro Evaluation of Mesalazine 400 mg Delayed Release Tablet for Colon Specific Delivery

Ulcerative colitis is a chronic inflammatory disease, and patients would get benefit more if the drug is given directly to the colon. Mesalazine is intended to deliver to the colon for treating ulcerative colitis. Here, we aimed to design and optimize mesalazine 400 mg delayed release tablet for colon-specific delivery using a quality by design (QbD) approach. The tablet was first formulated as an optimized core tablet and then coated with Eudragit S 12.5 for ensuring colonic delivery. The experimental design for the core tablet was constructed using a 32 full factorial design, where the percentages of sodium starch glycolate (SSG) and polyvinylpyrrolidone (PVP K-30) were independent variables and the tablet hardness (kg/cm2) and cumulative percentage of drug release at pH 7.2 phosphate buffer after 1.5 hours were treated as responses. Responses obtained from the initial exploratory formulations were evaluated to develop an optimized formulation to have a hardness value of 7-8 kg/cm2 and the maximum amount of drug release at pH 7.2 buffer. The optimized formulation involved the use of SSG and PVP K-30 at 3.05% and 1.69%, respectively. Hardness and cumulative percent of drug release obtained for the optimized core tablet were 7.8 kg/cm2 and 91.76%, respectively. The compatibility of drug and excipients was studied utilizing XRD, FTIR and TGA. The optimized core tablet was then coated with Eudragit S 12.5 to deliver the drug selectively to the colon and further assessed for its in vitro dissolution. Dissolution studies indicated that coated tablets with a weight gain of 7.4% exhibited the maximum cumulative percent of drug release (91.19 ± 0.11%), with a zero-order drug release profile (R2 = 0.943). A stability study performed according to ICH Q1A (R2) guidelines at accelerated storage conditions identified that there was no significant change in drug content over the storage period, indicating the stability of the formulated tablet batches. Together, these data suggest that the mesalazine tablet developed through the QbD approach offers excellent physical properties and drug release profile and, therefore, could be recommended for commercial manufacturing. Dhaka Univ. J. Pharm. Sci. 22(2): 189-201, 2023 (December)

One-component lipidic bicontinuous nanospheres as a smart drug loading platform to eradicate candida biofilms in oral and vaginal infection

Bicontinuous nanospheres (BCNs) with a highly twisted network of hydrophobic phases interwoven with a network of hydrated hydrophilic parts are essential for the loading and releasing of therapeutics. However, a facile methodology to construct BCNs with a single lipid molecule is still challenging. Here we report the synthesis of X-shaped lipids that can self-assemble into stable one-component sponge-phase BCNs without the assistance of any stabilizers as a platform for drug delivery. The X-shaped lipids with two hydrophilic heads and two hydrophobic tails are formed via dynamic covalent boronate between the phenylboronic acid-modified polar head and the catechol-containing lipids with different carbon chain lengths. This methodology provides an efficient and convenient way to synthesize lipids with different architectures, and their possibility in fabrication BCNs was further screened. The representative miconazole-loaded prodrug BCNs possess high drug loading content, up to 41.6%, and a fast, zero-order drug release profile after exposure to an acidic/oxidative microenvironment, such as Candida albicans biofilm. Also, the carbon chain lengths of lipids affect the prodrug BCNs' formation and interactions with fungal membranes. The optimal prodrug BCNs with 10-carbon chains hold superb Candida biofilm eradication efficacy in vitro and in vivo without affecting the normal tissues. Therefore, our strategy provides a facile methodology to construct BCNs as a smart drug loading platform for biomedical applications.

Supercritical Solution Impregnation of naproxen into mesoporous SiO2 SBA-15

Naproxen was impregnated into mesoporous SiO2 SBA-15 using the Supercritical Solution Impregnation (SSI) technique. Experiments were performed at 50–70ºC and 15–25 MPa in pure CO2 and CO2 modified with ethanol, ethyl acetate and menthol. Materials were also impregnated from liquid solutions in ethanol and chloroform. In the SSI experiments, naproxen was deposited on the internal surface of the mesopores as shown by N2-adsorption experiments. The percentage of naproxen impregnated decreased from 11.1% to 7.4% mass as the CO2 density increased. Likewise, adding ethanol, ethyl acetate or menthol to CO2 decreased the percentage of naproxen adsorbed on the support. Thermal analysis showed that naproxen impregnated on SiO2 by SSI became amorphous. FTIR and XRD confirmed the loss of crystallinity of naproxen and its interaction with the SiO2 support. Samples impregnated in liquid medium however kept partially their crystallinity. Release tests of naproxen on SiO2 SBA-15 prepared by SSI followed an almost zero-order release profile; the drug is released at a constant rate into a PBS pH= 7.4 medium. The release rate slowed down in comparison to that of pure naproxen, due to the interaction of the drug with the support and the diffusion of the drug outside the support mesopores. Thus, a sustained release system was achieved, which may help to attain a longer therapeutic effect with a lower naproxen dose.

Hydrocaffeic acid-chitosan coating of gastric patch provides long-acting mucoadhesive delivery of model chemotherapeutic agent

The development of a long-acting orally administered dosage form is a challenge. Here, we report development of a multi-layered mucoadhesive gastric patch that could deliver entrapped chemotherapeutic agent for eight days after oral administration. The multi-layered patch was designed to contain core layer, mucoadhesive layer and backing layer. The core layer contained the model chemotherapeutic agent, regorafenib. The mucoadhesive layer made of chitosan-hydrocaffeic acid conjugate showed greatest mucoadhesion strength of 18.1 ± 0.78 kPa in freshly excised rat gastric mucosa. The backing layer made of hydrophobic polycaprolactone-polydimethylsiloxane composite showed the contact angle of 120 ± 4.7° after placement of water drop. The entrapped regorafenib predominantly released from the mucoadhesive-side of the patch into simulated gastric fluid and showed a zero-order release profile. The patches were found to be stable for desired characteristics for up to 3 months in long term storage conditions. The pharmacokinetic studies in rat model revealed constant plasma concentration of regorafenib sustained for 8 days after oral administration of gastric patch. The gastric tissue where the patch adhered for 8 days did not show any significant histological changes compared with the normal gastric tissue. The oral administration of single dose of regorafenib-loaded gastric patch in FaDu cell xenografted tumor bearing athymic nude mice has shown significant (P < 0.05) reduction in the tumor volume over 7 days compared to the control group. Taken together, the multi-layered mucoadhesive gastric patch can be developed as a long-acting oral drug delivery system.

L-Cysteine Modified Chitosan Nanoparticles and Carbon-Based Nanostructures for the Intranasal Delivery of Galantamine.

The present study evaluates the use of thiolized chitosan conjugates (CS) in combination with two fundamental carbon nanoforms (carbon dots (CDs) and Hierarchical Porous Carbons (HPC)) for the preparation of intranasally (IN) administrated galantamine (GAL) nanoparticles (NPs). Initially, the modification of CS with L-cysteine (Cys) was performed, and the successful formation of a Cys-CS conjugates was verified via 1H-NMR, FTIR, and pXRD. The new Cys-CS conjugate showed a significant solubility enhancement in neutral and alkaline pH, improving CS’s utility as a matrix-carrier for IN drug administration. In a further step, drug-loaded NPs were prepared via solid-oil–water double emulsification, and thoroughly analyzed by SEM, DLS, FTIR and pXRD. The results showed the formation of spherical NPs with a smooth surface, while the drug was amorphously dispersed within most of the prepared NPs, with the exemption of those systems contianing the CDs. Finally, in vitro dissolution release studies revealed that the prepared NPs could prolong GAL’s release for up to 12 days. In sum, regarding the most promising system, the results of the present study clearly suggest that the preparation of NPs using both Cys-CS and CDs results in a more thermodynamically stable drug dispersion, while a zero-order release profile was achieved, which is essential to attain a stable in vivo pharmacokinetic behavior.

Design, development and characterization of interpenetrating polymer network hydrogel bead for controlled release of glipizide drug

In the current study, a novel interpenetrating polymer network (IPN) hydrogel bead was developed by encapsulation of antidiabetic drug glipizide using sodium alginate (SAL) and xanthan gum (XAG) biopolymers by ionotropic gelation technique with calcium chloride as cross-linking agent. In light of the fact that IPN hydrogel beads possess greater benefits in controlling the release of such short acting drug, sodium alginate and xanthan gum IPN hydrogel beads were prepared at different mass ratios (SAL:XAG = 10:0, 9:1, 8:2, 7:3, 6:4, 5:5). Similarly, drug-loaded IPN hydrogel beads were also developed. The prepared hydrogel beads were investigated using Fourier transform infrared spectroscopy, X-ray powder diffraction, and thermogravimetric studies to understand the type of interactions between the composite beads. Surface morphology changes were studied by scanning electron microscopy. The particle size, drug entrapment efficiency, and swelling behavior of prepared hydrogel beads were also studied. Based on in vitro drug dissolution studies, it was observed that SXF4 preparation containing SAL and XAG polymers at 7:3 ratio showed extended drug release of 97.53% at 9 h. This study demonstrated that inclusion of XAG has extended the drug release and able to achieve zero-order drug release profile.

Thermosensitive hydrogel loaded with biosynthesized silver nanoparticles using Eucalyptus camaldulensis leaf extract as an alternative treatment for microbial biofilms and persistent cells in tissue infections

Biofilms play a key role in the development of chronic tissue infections and antimicrobial resistance. In situ-forming thermosensitive hydrogel containing biosynthesized silver nanoparticles using aqueous Eucalyptus camaldulensis leaf extract (bio-AgNPs) was developed as an efficient anti-biofilm agent with a sustained release for tissue infection treatment. The formulation with 24% poloxamer 407, 5% poloxamer 188, and 1% hydroxypropyl methylcellulose demonstrated gelation temperature at 33 °C and homogeneous dispersion of bio-AgNPs throughout three-dimensional networks. Pharmaceutical properties of bio-AgNPs-loaded hydrogel presented shear-thinning behavior and zero-order release profile. The formulation showed broad-spectrum antimicrobial activity and comparable effects with existing antibiotics against important pathogens, including Gram-positive, Gram-negative bacteria, and fungi. The formulation at 1/8–1/2 minimum inhibitory concentrations (MIC) significantly inhibited biofilm production in all tested pathogens (p < 0.05). Confocal laser scanning microscopy images clearly illustrated dead cells within mature biofilm upon the treatment with the formulation at 2MIC for 4 h. The formulation effectively scavenged free radicals and decreased nitric oxide production up to 98%. Decrease in mRNA levels of inflammation-related enzymes and pro-inflammatory cytokines in lipopolysaccharide-stimulated RAW 264.7 cells confirmed the formulation as a potential anti-inflammatory agent. The findings suggested that bio-AgNPs-loaded hydrogel represents a promising therapeutic approach for tissue infections.

Everolimus immobilisation using polydopamine intermediate layer on poly(l-lactic acid)/poly(d-lactic acid) scaffold for sustainable anti-proliferative drug release

Drug-eluting stent (DES) is a widely used treatment to treat atherosclerosis with the incorporation of drugs within/coated on stents. Everolimus is one of the utilised anti-proliferative drugs in developing commercialised DES. However, long-term implantation of DES has contributed to late-stent thrombosis due to rapid release of drug. Therefore, a method such as chemical cross-linking intermediate layer should be adopted in the coating development to sustain the release of drugs. In this work, everolimus was immobilised on polymeric scaffolds of poly(l-lactic acid)/poly(d-lactic acid) (PLLA/PDLA) using a polydopamine (PDA) intermediate layer for possible application in DES development. PDA is known for its stability of cross-linking bonds which is beneficial to sustain drug release. In this study, the PLLA/PDLA scaffolds were grafted with the PDA intermediate layer and immobilised with different everolimus concentrations (0.01, 0.05 and 0.10 mM). The ability of PDA to covalently immobilise everolimus was demonstrated through ATR-FTIR, XPS, SEM, AFM, wettability and everolimus quantification. While the sustain release of everolimus was verified through the analyses of drug release and coating stability. The everolimus was successfully immobilised on the PDA layer through O–N and C–O covalent linkages. The flowery-structured everolimus was observed with lower wettability and higher roughness on the greater concentration of everolimus. A sustainable drug release profile was acquired following the zero-order release profile for the 0.05 mM and 0.10 mM everolimus concentrations. The higher everolimus concentration produced greater contribution on the coating stability. These results indicate the capability of PDA to mediate the everolimus immobilisation for sustainable drug release, which is a potential approach in resolving the complication of current DES.

Sustained Release Biocompatible Ocular Insert Using Hot Melt Extrusion Technology: Fabrication and in-vivo evaluation

Topical eye drops usually have low bioavailability of the drug. Rapid turnover of lacrimal fluid flushes the drug away from the ocular surface, and the drug has limited time for absorption. Therefore, we design Metoprolol loaded ocular insert to enhance bioavailability against glaucoma in this study. Hot-melt extrusion was utilized to prepare the inserts using Gelatin, GelMa, and Polyacrylic acid (PAA) as matrix-forming polymers. The prepared ocular insert was characterized for physicochemical properties and in vitro drug release. It was observed that GelMa concentration and PAA concentration greatly affected drug release. Inserts prepared from Gelatin-PAA released 38.6% Metoprolol in the first hour. However, replacing 20% of Gelatin with GelMa reduced the initial release to 23.6%.Moreover, inserts prepared with 30% GelMa released 19% of the drug in the first hour, which exhibited a quasi zero-order release profile. The effect of PAA concentration on the release of the drug was also very evident. Inserts prepared with 5% PAA concentration released around 30% of the drug in the first hour, while those prepared with 20% PAA took 2 h to release a similar amount of drug. Similarly, 81% and 50% of the drug were released after 4 h from inserts containing 5% PAA and 20% PAA, respectively. Thus, it is clear that Metoprolol release can be tuned by varying the GelMa and PAA concentration in the formulation. The insert, which was able to sustain the drug release for 12 h, has the potential to be used as a good ocular delivery system, which requires less frequent dosing compared to eye drops.

In vitro & in vivo evaluations of PLGA nanoparticle based combinatorial drug therapy for baclofen and lamotrigine for neuropathic pain management

Aim Baclofen and Lamotrigine via PLGA nanoparticles were developed for nose-to-brain delivery for the treatment of Neuropathic pain. Methods Nanoparticles were prepared using the modified nano-precipitation method. The prepared NPs were characterised and further in vitro and in vivo studies were performed. Results The Bcf-Ltg-PLGA-NPs were ∼177.7 nm with >75%(w/w) drugs encapsulated. In vitro dissolution studies suggested zero-order release profiles following the Korsmeyer-Peppas model. In vitro cytotoxicity and staining studies on mammalian cells showed dose dependant cytotoxicity where nanoparticles were significantly less toxic (>95% cell-viability). ELISA studies on RAW-macrophages showed Bcf-Ltg-PLGA-NPs as a potential pro-inflammatory-cytokines inhibitor. In vivo gamma-scintigraphy studies on rats showed intra-nasal administration of 99mTc-Bcf-Ltg-PLGA-NPs showed C max 3.6%/g at T max = 1.5h with DTE% as 191.23% and DTP% = 38.61% in brain. Pharmacodynamics evaluations on C57BL/6J mice showed a significant reduction in licks/bites during inflammation-induced phase II pain. Conclusion The findings concluded that the combination of these drugs into a single nanoparticle-based formulation has potential for pain management.

Preparation and characterizations of glyceryl oleate ufasomes of terbinafine hydrochloride: a novel approach to trigger Candida albicans fungal infection

BackgroundWorldwide fungal infection cases are increasing by leaps and bounds. The patients who are immunocompromised, i.e., cancer and AIDS, are more susceptible to different types of fungal infections like cutaneous candidiasis and its associate infections. The available treatment for such a disease is creams, gels, etc. However, due to the lack of penetrability and higher systematic absorption, these formulations have reported many side effects. To overcome such challenges, various novel drug delivery systems were introduced. The present research focused on the preparation of glyceryl oleate ufasomes of terbinafine hydrochloride using the film hydration method.ResultThe prepared formulations were characterized for globular size (nm), zeta potential (mV), PDI, morphological characteristics, thermal behavior, in vitro drug release, in vitro antifungal activity, and in vitro skin permeation retention studies. After suitable formulation optimization using thin-film hydration method, 3:7 drug to glyceryl oleate ratio, UF3 formulation was found to produce higher drug entrapment efficacy (52.45 ± 0.56%), stable anionic zeta potential (− 33.37 ± 0.231 mV), desired globular size (376.5 ± 0.42 nm), and decent polydispersity index (0.348 ± 0.0345). Diffusion-controlled and zero-order sustained release profile was observed in the optimized UF3 batch. From the 5 days in vitro antifungal activity studies, it confirmed that UF3 ufasomes possessed good applicability in more prolonged therapy.ConclusionFrom the current investigation, it can be concluded that glyceryl oleate ufasomes of terbinafine hydrochloride could be an excellent approach to treat topical fungal infections.

Novel bind-then-release model based on fluorescence spectroscopy analysis with molecular docking simulation: New insights to zero-order release of arbutin and coumaric acid

The present study aimed to systematically investigate the mechanisms of the zero-order release of arbutin and coumaric acid from whey protein concentrate-high methoxyl pectin (WPC-HMP) complex. The morphological analysis was applied to characterize the structure of the complexes, and fluorescence spectroscopy analysis with molecular docking simulation was used to study their binding interactions. The results indicated that porous structure of WPC-HMP with average pore diameter of 29.02 μm had no influence on the release profiles. The binding constant of coumaric acid (8.71 × 104 L/mol) was higher than that of arbutin (2.90 × 104 L/mol) at 298 K, led to the priority in binding order of coumaric acid. The main binding affinities were van der Waals forces and hydrogen bonds for arbutin, but hydrophobic interactions for coumaric acid. The binding interactions also resulted in regular conformational and structural changes of WPC. Moreover, a novel bind-then-release model for arbutin and coumaric acid was developed, revealing the final zero-order release profile is the balance between the competition effect and the diffusion effect.

3D Printing of Tunable Zero-Order Release Printlets.

Zero-order release formulations are designed to release a drug at a constant rate over a prolonged time, thus reducing systemic side effects and improving patience adherence to the therapy. Such formulations are traditionally complex to manufacture, requiring multiple steps. In this work, fused deposition modeling (FDM) 3D printing was explored to prepare on-demand printlets (3D printed tablets). The design includes a prolonged release core surrounded by an insoluble shell able to provide zero-order release profiles. The effect of drug loading (10, 25, and 40% w/w paracetamol) on the mechanical and physical properties of the hot melt extruded filaments and 3D printed formulations was evaluated. Two different shell 3D designs (6 mm and 8 mm diameter apertures) together with three different core infills (100, 50, and 25%) were prepared. The formulations showed a range of zero-order release profiles spanning 16 to 48 h. The work has shown that with simple formulation design modifications, it is possible to print extended release formulations with tunable, zero-order release kinetics. Moreover, by using different infill percentages, the dose contained in the printlet can be infinitely adjusted, providing an additive manufacturing route for personalizing medicines to a patient.

A molecular understanding of magnesium aluminium silicate – drug, drug – polymer, magnesium aluminium silicate – polymer nanocomposite complex interactions in modulating drug release: Towards zero order release

This study reports the use of ITC in understanding the thermodynamics occurring for a controlled release system in which complexation has been exploited. In this study, a model drug, propranolol hydrochloride (PPN) was complexed with magnesium aluminium silicate (MAS) and these complexes were used in combination with polyethylene oxide (PEO) as a hydrophilic carrier at various concentrations to sustain the release of PPN. DSC, XRPD, ATR-FTIR and SEM/EDX were successfully used in characterising the produced complexes. 2D- SAXS data patterns for MAS and the produced complexes were shown to be symmetric and circular with the particles showing no preferred orientation at the nanometre scale. ITC studies showed differences between PPN adsorption onto MAS compared with PPN adsorption onto a MAS-PEO mixture. At both temperatures studied the binding affinity Ka was greater for the titration of PPN into the MAS-PEO mixture (5.37E + 04 ± 7.54E + 03 M at 25 °C and 8.63E + 04 ± 6.11E + 03 M at 37 °C), compared to the affinity obtained upon binding between PPN and MAS as previously reported suggesting a stronger binding with implications for the dissolution process. MAS-PPN complexes with the PEO polymer compacts displayed desired manufacturing and formulation properties for a formulator including, reduced plastic recovery therefore potentially reducing the risk of cracking/splitting and on tooling wear, controlled release of PPN at a significantly low (5%) polymer level as well as a zero-order release profile (case II transport) using up to 50% polymer level.

Drug Release from a Spherical Matrix: Theoretical Analysis for a Finite Dissolution Rate Affected by Geometric Shape of Dispersed Drugs

Amending the neglect of finite dissolution in traditional release models, this study proposed a more generalized drug release model considering the simultaneous dissolution and diffusion procedure from a drug-loaded spherical matrix. How the shape factor (n = 0, 1/2, and 2/3 for the planar, cylindrical, and spherical geometry, respectively) of dispersed drug particles affected the release from the matrix was examined for the first time. Numerical solutions of this generalized model were validated by consensus with a short-time analytical solution for planar drugs and by the approach of the diffusion-controlled limits with Higuchi’s model. The drug release rate increases with the ratio of dissolution/diffusion rate (G) and the ratio of solubility/drug loading (K) but decreases with the shape factor of drug particles. A zero-order release profile is identified for planar drugs before starting the surface depletion layer, and also found for cylindrical and spherical dispersed drugs when K and G are small, i.e. the loaded drug is mainly un-dissolved and the drug release rate is dissolution-controlled. It is also shown that for the case of a small G value, the variation of drug release profile, due to the drug particle geometry, becomes prominent. Detailed comparison with the results of the traditional Higuchi’s model indicates that Higuchi’s model can be applied only when G is large because of the assumption of an instantaneous dissolution. For K = 1/101–1/2, the present analysis suggests an error of 33–85% for drug release predicted by Higuchi’s model for G = 100, 14–44% error for G = 101, while a less than 5% error for G ≧ 103.

Sustained release from biodegradable metallic matrix—The entrapment of drugs within iron

Iron and its alloys have been widely used for variety of medical implants. These are used for long term applications as cheap implants with high inertness and low corrosion rate, and also as implants with high biocompatibility (the fourth-generation type). Such degrading implants can provide a temporary scaffold while the body heals. In addition to the needed mechanical support, it is highly desirable to provide local drug therapy, providing antibacterial properties, preventing rejection of the implant, and more. So far, the combination of a degradable metallic implant which serves also as a three-dimensional matrix for drug release, remained un-answered. Here we present, we believe for the first time realization of this concept: Entrapment of drugs within a 3D degradable metal matrix—iron—from which the entrapped drugs are sustain-released. This new type of material is based on the molecular metals entrapment materials methodology, resulting in drugs@Fe. Two drugs have been successfully entrapped and released: chlorhexidine - an antiseptic drug, and rapamycin—used for avoiding transplant rejection. The delivery profiles of the composites were studied in two forms—powders and pressed discs showing two different types of drug release profiles. The release of the drugs from the powder hasa first order release profile, while the pressed disk is a slower, zero-order release profile, which is highly desirable due to the constant rate of the release. Full characterization of the metallic biomaterials is provided, including XRD, SEM, TGA, elemental analysis, and surface area/porosity analysis.

The DESIGN AND DEVELOPMENT OF CARVEDILOL GASTRORETENTIVE FLOATING DRUG DELIVERY SYSTEMS USING HYDROPHILIC POLYMERS AND IN VITRO CHARACTERIZATION

Objective: The primary aim of the present examination was to create carvedilol phosphate floating tablets using factorial designs and for retention in the upper portion of the gastrointestinal (GI) tract to sustain the dissolution where the solubility of carvedilol phosphate is more in an acidic medium.&#x0D; Methods: The floating tablets of carvedilol phosphate were ready to employ different concentrations and a combination of these polymers of Na-alginate, Carbopol 934P, and sodium carboxymethyl cellulose (NaCMC) with lubricants magnesium stearate by direct compression technique. In the present experiment, involved sodium bicarbonate and citric acid as a gas-producing agent. Fifteen formulations structured and judged for pre-compression components like the angle of repose, bulk and tapped density, Hausner’s ratio, compressibility index, and post-compression factors are weight uniformity, hardness, drug content, friability, in vitro buoyancy, dissolution studies, and Fourier transforms infrared spectroscopy (FTIR).&#x0D; Results: The drug released 90.02% in 12 h by combining NaCMC (7.5 mg) and Na-alginate (7.5 mg) in the formulation F14 towards the achievement of sustained release. Batch F14 selected as optimized, as provided desired zero-order release profile as well as floating lag time 20 s and total floating time&gt;12 h, and the mechanism of drug release observed (n = 1.098, super case-II transport).&#x0D; Conclusion: From the results fulfilled that all the preparation found to be within the pharmacopeia limits and was the best dosage form to treat moderate heart failure and hypertension. The in vitro dissolution profiles of all formulations placed into various kinetic models, the statistical parameters like slope, regression coefficient and intercept determined. The gastro-retentive dosage form to maintain the sustain drug delivery, which would improve the maximum therapeutic efficacy and patient compliance.

A nanofiber-based drug depot with high drug loading for sustained release

Nanostructures and their related structure-performance relationships for "efficacious, safe and convenient" drug delivery are playing a more and more important role in the fast development of nanopharmaceutics. In this study, a core-shell fiber based nano depot (ND) is prepared for achieving a high drug loading and meanwhile ensuring a zero-order drug sustained release profile. With cellulose acetate (CA) as a filament-forming polymeric matrix and ferulic acid (FA) as a model drug, a triaxial electrospinning was implemented to generate the ND. An elaborate strategy was exploited to ensure a continuous, robust and effective preparation. The strategy comprised a solvent mixture as the outer fluid, a mixed solution containing FA and CA with a high CA concentration as the spinnable middle fluid, and a pure drug solution as the inner liquid for loading enough FA in the NDs as much as possible. TEM and SEM demonstrated the core-shell structure of NDs. The NDs had a drug loading of 71.5±4.6%. The in vitro dissolution tests demonstrated that the loaded FA was able to release through a zero-order kinetics of Q (FA released percentage) to t (release time): Q=12.03+1.89t (R=0.9928) during the 48h. Only 3.6% of the loading FA was released during the late tailing-off period. Three different diffusion types about the drug sustained release mechanism are suggested.

Ethylcellulose-based drug nano depots fabricated using a modified triaxial electrospinning

New strategies based on advanced technologies are highly desired for expanding the applications of biological macromolecules in the applied scientific fields. In the present study, a new kind of core-shell nano depots were designed, in which the shell section was a drug-polymer composite and the core section was a drug reservoir. With ethyl cellulose and ketoprofen as a filament-forming polymeric matrix and a model drug, respectively, a triaxial electrospinning apparatus was developed to conduct both coaxial and triaxial processes, by which monolithic nanofibers F1 and core-shell nano depots F2 were successfully prepared. Although both of them had the same double components, their different nanostructures generated considerable differences in providing drug sustained release profiles. The core-shell nanofiber depots F2 were able to provide a better zero-order drug release profile: no initial burst release, smooth sustained release effect, and smaller tailing-off release for a nice zero-order drug release kinetics. The release percentage (Q) can be linearly manipulated through the release time (t) according to the equation Q2 = 9.40 + 4.74 t (R = 0.9936), providing opportunity for precise administration. The developed strategy and advanced electrospinning technique exhibit a new way for constructing process-structure-performance relationships at nano scale and for expanding the potential applications of biological macromolecules in the applied fields.