Controlled Release Formulations Research Articles

Study on physical properties of four pH responsive Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) microcapsules as controlled release carriers

This study provides a promising controlled release form of nuclear polyhedrosis virus (NPV) for targeted control of lepidopteran pests. However, the application of NPV is limited due to its sensitivity to UV inactivation. This study investigated the anti-UV properties of microcapsules of SeMNPV occlusion bodies (OBs) encapsulated by calcium alginate (CA), and also the influence of the modification of CA by chitosan (CS), whey protein (WP), and polydopamine (PDA). These capsules were used to deliver, in a controlled release manner virions under alkaline pH conditions. Characterization of the structure, morphology, particle size, encapsulation efficiency, contact angle, insecticidal activity, UV resistance and in vitro release of the microcapsules was conducted. The modified microcapsules had better sphericity, and were devoid of SeMNPV OBs on the surface. The encapsulation rate was 84.76 ± 0.59%. PDA@CA-NPV had the highest wettability and the contact angle was 74.51 ± 0.53°. The 50% lethal concentration values (LC50) of CA-NPV, CS@CA-NPV, WP@CA-NPV and PDA@CA-NPV were 11.5, 10.7, 10.5 and 1.2 times that of SeMNPV OBs alone. The modified microcapsules all improved the anti-UV performance of the virus, and PDA@CA-NPV was the most UV-resistant. Using qPCR, it was observed that under alkaline conditions, a large number of virions were released from PDA@CA-NPV, CA-NPV and SeMNPV OBs. Microencapsulated virus under alkaline conditions did not change the release pattern of virions.

Degradable Self-Destructive Redox-Responsive System Based on Mesoporous Organosilica Nano-Vehicles for Smart Delivery of Fungicide

The development of stimuli-responsive controlled release formulations is a potential method of improving pesticide utilization efficiency and alleviating current pesticide-related environmental pollution. In this study, a self-destruction redox-responsive pesticide delivery system using biodegradable disulfide-bond-bridged mesoporous organosilica (DMON) nanoparticles as the porous carriers and coordination complexes of gallic acid (GA) and Fe(III) ions as the capping agents were established for controlling prochloraz (PRO) release. The GA-Fe(III) complexes deposited onto the surface of DMON nanoparticles could effectively improve the light stability of prochloraz. Due to the decomposition of GA-Fe(III) complexes, the nano-vehicles had excellent redox-responsive performance under the reducing environments generated by the fungus. The spreadability of PRO@DMON-GA-Fe(III) nanoparticles on the rice leaves was increased due to the hydrogen bonds between GA and rice leaves. Compared with prochloraz emulsifiable concentrate, PRO@DMON-GA-Fe(III) nanoparticles showed better fungicidal activity against Magnaporthe oryzae with a longer duration under the same concentration of prochloraz. More importantly, DMON-GA-Fe(III) nanocarriers did not observe obvious toxicity to the growth of rice seedlings. Considering non-toxic organic solvents and excellent antifungal activity, redox-responsive pesticide controlled release systems with self-destruction properties have great application prospects in the field of plant disease management.

Effect of different adjuvant formulations on the antibody response of horses to porcine zona pellucida proteins

Immunization with porcine zona pellucida (PZP) proteins is being used successfully to induce infertility in wildlife including horses. However, widespread adoption of this method to control the growth of horse populations requires further refinement in order to induce long-term infertility, reduce the frequency and severity of injection site reactions, and make the vaccines easier to administer. The next generation of PZP-based vaccines will likely be a controlled-release formulation with different adjuvants from the Freund’s adjuvants used in existing vaccines. We evaluated the response of equine peripheral blood mononuclear cells to a cationic nanoparticle adjuvant, Nano-11, alone and with the TLR agonists poly(I:C) and CpG ODN as a screen to develop an adjuvant system suitable for immunization of horses. The secretion of IL-1β, TNF and CXCL10 were used as readouts. The combination of poly(I:C) with Nano-11 significantly increased the secretion of IL-1β and TNF in comparison with Nano-11 only, with little effect of further addition of CpG ODN. The efficacy of the Nano-11/poly(I:C) adjuvant to enhance the immune response to native PZP proteins was determined in horses. Horses were immunized twice with the licensed Zonastat-H vaccine or PZP with Nano-11/poly(I:C) emulsified in silicone oil. A third group received PZP with the saponin adjuvant QA-21 emulsified in silicone oil. The horse sera collected monthly after the injections had increased anti-PZP IgG antibodies with the strongest response observed with Zonastat-H. We conclude that Nano-11/poly(I:C) is a potential candidate for the development of a controlled release formulation of a next generation PZP-based immunocontraception.

Effect of phosphatidylcholine in bentonite-quetiapine complex on enhancing drug release and oral bioavailability

Bentonite (BT) is a biocompatible clay mineral that has advantageous properties as a pharmaceutical excipient. However, the application of BT in controlled-release oral formulations has been challenging due to incomplete drug release from BT-drug complexes. The objective of this study was to investigate the effect of modifying BT with zwitterionic phosphatidylcholine (PC) to enhance the dissolution of drugs, thereby increasing their oral bioavailability. Quetiapine (QTP) was chosen as a model drug, and the composition of the complex (BT-PC-QTP) was optimized to have the maximum QTP content and increase the total amount of QTP released. The in vitro release study showed that the incorporation of an appropriate amount of PC into BT improved the low release rate of the BT-QTP complex at pH 7.4, while the pH-dependent release property of BT was maintained. In an in vivo pharmacokinetic study in rats, the oral administration of the BT-PC-QTP complex showed significantly higher Cmax and AUC values than the BT-QTP complex. Moreover, BT-PC-QTP showed a 2.4-fold enhancement of oral bioavailability compared to the QTP powder group. The scanning electron microscopy (SEM), powder X-ray diffraction (pXRD), and differential scanning calorimetry (DSC) studies confirmed that the intercalation of PC and QTP into BT resulted in the adsorption of QTP in an amorphous state. The characterization of the nanoparticles generated from the BT-PC-QTP complex supported that PC enhanced the dissolution of QTP by forming nanosized PC particles. Taken together, the modification of BT with PC can be applied in pharmaceutical industry as a platform strategy to control the release of the BT-drug complex and enhance the oral bioavailability of poorly water-soluble drugs.

Development and Evaluation of Etodolac Osmotic Capsule

controlled release formulations have been developed based on their significant advantages over conventional immediate release dosage forms, such as the decrease of dosing frequency, the increase of patient compliance, better dosing patterns, the reduction of side effects, or the maintenance of the drug concentration within a desired range, i.e., an overall improved therapeutic benefit. However, oral controlled release formulations are exposed to changing environment during transit through the GI-tract which may affect their performances e.g. physiological factors such as patient age or food-intake. Reported as releasing drug independently of these factors, oral osmotically-driven systems (OODS) have taken an integral place in the pharmaceutical field. The dissolution profile of orally delivered drugs can be controlled through the use of osmotically controlled drug delivery devices. The most commonly used device is the osmotic tablet/Capsule, which is essentially a tablet/Capsule core that is coated with a rate-limiting semipermiable membrane. Using osmotic pressure as driving force, various OCODDS design and compositions have been developed. Numerous products are launched based on these systems. In present investigation attempts are taken to formulate, optimize and develop an economic osmotically controlled Capsule containing drugs belonging to non steroidal anti-inflammatory category to release the drug in controlled manner. Such formulations are most beneficial for the patients shifted on long term pain management therapy(e.g. in arthritis) in view to reduce the associated side effects of these drugs.

CMC based microcapsules for smart delivery of pesticides with reduced risks to the environment

Inefficient use of traditional pesticides causes serious environmental pollution. Stimuli-responsive pesticide formulations improve the utilization efficiency of target pests and reduce harm to non-target organisms and the environment. Herein, multi-stimuli-responsive avermectin (AVM) polyurea microcapsules (AVM@CM-SS-PU) are prepared by interfacial polymerization with modified carboxymethyl cellulose CMC-SS-NH2 as the wall material and hexadecane as the temperature-responsive core. The microcapsules are 3.90 μm in size and the encapsulation efficiency of AVM is 88.23 %. The photostability of AVM@CM-SS-PU is 5-times that of AVM solution. The insecticidal effect of AVM solution and AVM emulsifiable concentrate (EC) decreases to 13.3 % and 16.6 %, respectively, after UV irradiation for 180 min, whereas that of AVM@CM-SS-PU still remains at 50.0 %. AVM@CM-SS-PU has better foliar affinity and releases under the stimuli of temperature, glutathione, pH, cellulase, and urease. Hence, it has high insecticidal activity and biosafety. This smart controlled-release pesticide formulation provides a promising solution for green agriculture.

PH/redox/α-amylase triple responsive metal-organic framework composites for pest management and plant growth promotion

The development of stimuli-responsive controlled release formulations is a promising strategy to enhance the utilization efficiency and reduce the environmental pollution of pesticides. In this work, a smart pH/redox/α-amylase triple stimuli-responsive pesticide delivery system was constructed by bonding carboxymethyl starch (CMS) with metal-organic frameworks (MIL-101(Fe)–NH2 nanoparticles) which loaded with CAR (CAR@MIL-101(Fe)-CMS nanoparticles). The results indicated that the loading capacity of CAR@MIL-101(Fe)-CMS nanoparticles for CAR was approximately 18.3% and the CMS attached on the surface of CAR@MIL-101(Fe)–NH2 nanoparticles could protect CAR from photolysis effectively. Meanwhile, the coated CMS and metal-organic framework structure of the nanoparticles could be decomposed and consequently release pesticide active ingredients on demand when CAR@MIL-101(Fe)-CMS nanoparticles were metabolized by glutathione and α-amylase in the insect alkaline midgut. The bioactivity survey confirmed that CAR@MIL-101(Fe)-CMS nanoparticles had a longer duration in controlling Spodoptera frugiperda larvae compared to CAR suspension concentrate. In addition, the MIL-101(Fe)-CMS nanocarriers were safe for the growth of maize and could be used as fertilizer to promote the growth and development of crops. Thus, this smart stimuli-responsive pesticide-fertilizer all-in-one combination strategy has great potential in pest management.

Release Kinetics of Hydroxypropyl Methylcellulose Governing Drug Release and Hydrodynamic Changes of Matrix Tablet.

Hydrophilic Hydroxypropyl Methylcellulose (HPMC) matrix tablets are the standard role model of the oral controlled-release formulation. Nevertheless, the HPMC kinetics for the mechanistic understanding of drug release and hydrodynamic behaviors are rarely investigated. This study aims to investigate the release behaviors of both HPMC and paracetamol (model drug) from the hydrophilic matrix tablet. Two different viscosity grades of HPMC were used (Low viscosity: 6 cps, High viscosity: 4,000 cps). Three different ratios of drug/HPMC (H:38.08%, M:22.85%, and L:15.23% (w/w) of HPMC amounts in total weight) matrix tablets were prepared by wet granulation technique. The release profiles of the drug and HPMC in a matrix tablet were quantitatively analyzed by HPLC and 1H-Nuclear Magnetic Resonance (NMR) spectroscopy. The hydrodynamic changes of HPMC were determined by the gravimetric behaviors such as swelling and erosion rates, gel layer thickness, front movement data,and distributive Near-Infrared (NIR) chemical imaging of HPMC in a matrix tablet during the dissolution process. High viscosity HPMC tablets showed slower release of HPMC than the release rate of drug, suggesting that drug release preceded polymer release.Different hydration phenomenon was qualitatively identified and corresponded to the release profiles. The release behaviors of HPMC and drug in the tablet could be distinguished with the significant difference with fitted dissolution kinetics model (Low viscosity HPMC 6cps; Korsmeyer-Peppas model, High viscosity HPMC 4000cps; Hopfenberg model, Paracetamol; Weibull model) according to the weight of ingredients and types of HPMC. The determination of HPMC polymer release correlating with drug release, hydrodynamic behavior, and NIR chemical imaging of HPMC can provide new insights into the drug release- modulating mechanism in the hydrophilic matrix system.

Microencapsulation of Bacillus velezensis Using Alginate-Gum Polymers Enriched with TiO2 and SiO2 Nanoparticles.

Bacillus bacteria are a group of plant growth stimulants that increase plant growth and resistance to plant pathogens by producing various metabolites. With their large surface area and small size, nanoparticles can be used in controlled-release formulations and increase the efficiency of the desired product. Encapsulation of biological agents in combination with nanoparticles can be an essential step in increasing the performance of these agents in adverse environmental conditions. In this study, which is the result of a collaboration between scientists from Italy and Iran, Bacillus velezensis was encapsulated in alginate combined with whey protein and zedo, mastic, and tragacanth gums in the presence of silica and titania nanoparticles to obtain two-layer and multilayer assemblies acting as novel, smart micro-encapsulation systems. The results of laboratory studies showed that the B. velezensis could produce protease, lipase, siderophore, auxin, and a dissolution of mineral phosphate. Scanning electron microscopy images (SEM) showed that the studied microcapsules were almost spherical. Moisture affinity, swelling, and efficiency of each microcapsule were examined. The results showed that the highest encapsulation efficiency (94.3%) was related to the multilayer formulation of alginate-whey protein-zedo. XRD and FTIR spectroscopy showed that the alginate, whey protein, and zedo were mixed properly and no incompatible composition occurred in the reaction. This study aimed to provide a suitable formulation of biofertilizers based on biodegradable compounds as an alternative to chemical fertilizers, which is low cost and very effective without harming humans and the environment.

Development and characteristics of layered EGCG/Montmorillonite hybrid: An oral controlled-release formulation of EGCG

An oral controlled-release formulation of epigallocatechin-3-gallate (EGCG) was developed by intercalating EGCG into the interlayer space of Food and Drug Administration-approved mucoadhesive montmorillonite (Mt) nanolayers, and characterized by ultraviolet–visible, X-ray diffraction, Fourier transform infrared, and thermogravimetry. The EGCG intercalation was only possible at acidic pH, and occurred through electrostatic and hydrogen bonding interactions allowing restacking of exfoliated Mt nanolayers with EGCG molecules. It was inferred that EGCG molecules were adsorbed flat on the interlayer surface of Mt in a monolayer and formed two-sided hydrogen bonds with the Mt faces, leading to a ∼2-fold increase in the EGCG decomposition temperature. A maximum EGCG loading of ∼40 wt% was achieved at pH 3, reaction time 1 h, and EGCG:Mt ratio 40:10 mg/mL. The EGCG/Mt hybrid showed a sustained release of EGCG in simulated gastric and intestinal fluids in a pH-dependent manner. Deprotonation of EGCG was responsible for further EGCG release at pH 7.4 compared to pH 1.2. The release profiles were fitted to the parabolic diffusion and Bhaskar models, implying that the release was controlled by a diffusion process. These results suggest that Mt with a high loading capacity can be used as the controlled-release nanocarrier of EGCG in oral administration.

Preparation and evaluation of the doxazosin-bentonite composite as a pH-dependent controlled-release oral formulation

Bentonite (BT) is a natural clay mainly composed of montmorillonite which has exchangeable cations in the interlayer space. BT has various advantages as a pharmaceutical excipient for the formulation of drug delivery systems (DDSs), including biocompatibility and unique physicochemical properties (i.e., adsorption and pH-dependent cation exchange). However, previous studies on the application of BT for DDSs were usually limited to the characterization of the in vitro adsorption and release properties. Herein, we prepared and characterized a doxazosin-bentonite (DXBT) composite formulation for controlled oral delivery and then evaluated the pharmacokinetics of doxazosin (DX) in rats. The composition of the DXBT composite was optimized based on the adsorption efficiency and the content of DX in the DXBT composite. The change in morphology was observed by scanning electron microscopy (SEM). Intercalation of amorphous DX between the BT interlayer space was confirmed by powder X-ray diffraction (pXRD). The zeta potential of DXBT composite was higher than BT over the pH range between 1 and 8, and was positive in acidic condition and was changed to negative at pH above 4. The DXBT composite showed pH-dependent in vitro release profiles of DX, and the cumulative release amount at 24 h was higher at pH 7.8 than at pH 1.2 and 7.4 (63.9, 29.3 and 47.8%, respectively). In an in vivo pharmacokinetic study after oral administration in rats, the DXBT composite resulted in a significantly lower peak plasma concentration (Cmax) and longer terminal half-life (t1/2) and mean residence time (MRT) of DX compared to DX solution. Thus, the DXBT composite could be an oral drug delivery platform with pH-dependent controlled-release profiles based on the unique ion-exchange property of BT.

Synthesis and Characterization of 2,4-Dichlorophenoxypropanoic Acid (2,4-DP) Herbicide Interleaved into Calcium-Aluminium Layered Double Hydroxide and the Study of Controlled Release Formulation

The commonly used herbicide in agriculture, namely 2,4-dichlorophenoxypropanoic acid (2,4-DP), is an anionic herbicide used to interleave into the interlayer of calcium-aluminum layered double hydroxide (Ca-Al LDH) employing co-precipitation method to form a new nanohybrid labeled as CAL-2,4DP. The LDH compound serves as a host in supporting the herbicide’s controlled release formulation. The effective interleave was investigated by employing a powder X-Ray Diffraction (XRD) pattern at 0.025 M nanocomposite, which revealed that the basal spacing has increased from 8.0 Å to 23.8 Å. The ATR-FTIR spectra further supported the interleaving, where the nitrate peak (NO−) diminished, and the carboxylate ion (COO−) band appeared at 1653 cm−1. The percentage loading of CAL-2,4DP was 71.26%, calculated from the carbon content in the sample. The BET analysis shows that CAL-2,4DP was a mesoporous material relying on nitrogen-desorption isotherms. The release of 2,4-DP ions into the aqueous solutions followed the order of PO43− > CO32− > Cl− with a percentage of 83, 65, and 30%, respectively. This work indicates the successful interleaving process of the 2,4-DP anion and the potential of CAL-2,4DP as an eco-friendly agrochemical that can be beneficial for farmers in minimizing herbicide usage to the environment.

Preparation and Insecticidal Activity Evaluation of Emamectin-Lignin Sulfonic Acid Conjugate with Antiphotolysis Property.

Controlled release formulations (CRFs) are considered an effective way to solve the low bioavailability of traditional pesticides. However, CRFs prepared by coating or encapsulation has the disadvantage of explosive release of the ingredients. Sustained-release pesticides prepared by coupling with a carrier can overcome this shortcoming. In the present study, an emamectin–lignin sulfonic acid conjugate (EB–SL), in which emamectin was connected via sulfonamide bonds with lignin, was prepared using sodium lignosulfonate as the carrier. The structure of the conjugate was characterized by IR, 1HNMR, and elemental analysis. The sustained-release results showed that EB–SL maintained its original structure when released in pure water and soil columns, and the sulfamide bond did not break. The photolysis test displayed that the photolysis half-life T0.5 of EB–SL was increased by 1.5 times compared with the emamectin suspending concentrate (EB-SC). Bioactivity tests in the greenhouse showed that EB–SL not only had similar insecticidal toxicity to emamectin emulsion concentrate (EB-EC) against Ostrinia nubilalis but also displayed a longer duration. The lethality of EB–SL on O. nubilalis was maintained at more than 70% across 19 days, whereas EB-EC as the control was less than 50% after 11 days of application.

A novel long-acting formulation of oral buprenorphine/naloxone produces prolonged decreases in fentanyl self-administration by rhesus monkeys

BackgroundDue to the poor oral bioavailability of buprenorphine, an oral formulation has not been thought possible. Lyndra Therapeutics is developing a once-weekly long-acting oral product containing buprenorphine. We evaluated the efficacy of this formulation in reducing intravenous (i.v.) fentanyl self-administration by three male and three female rhesus monkeys. MethodsBuprenorphine HCl and naloxone HCl were co-formulated using an 11:1 ratio of buprenorphine:naloxone in a controlled-release gastric residence formulation administered in an oral capsule (LYN-013). Naloxone was included to determine the feasibility of combining naloxone with buprenorphine in the formulation as an abuse deterrent. Complete fentanyl dose-response functions were determined during each session. The efficacy of single doses of 56/5, 112/10 and 168/15 mg buprenorphine/naloxone in reducing fentanyl self-administration was examined over 13 days. Results: LYN-013 significantly decreased the rate of responding for fentanyl for 3 days and significantly reduced total intake of fentanyl for 8 days. Time to maximal buprenorphine levels (Tmax) ranged between 56 and 68 h for all 3 doses. The maximal buprenorphine level (Cmax) following 168 mg was 2.3 ng/ml which was significantly greater that those observed for 56 mg (1.22 ng/ml) and 112 mg (1.35 ng/ml). Finally, the area-under-curves (AUCtau) were buprenorphine dose-dependently increased from 88 to 127–265 h*ng/ml. There were no signs of non-specific changes in behavior. ConclusionsA once-weekly oral buprenorphine/naloxone formulation produced sustained suppression of fentanyl self-administration in monkeys suggesting that oral delivery of buprenorphine with this formulation could provide a new opportunity to treat opioid use disorders (OUD).

Preparation and In Vitro Evaluation of Controlled-Release Matrices of Losartan Potassium Using Ethocel Grade 10 and Carbopol 934P NF as Rate-Controlling Polymers.

Controlled-release formulations are essential for those drugs that require fine tuning of their activity to increase the ratio between therapeutic vs. adverse effects. Losartan potassium is among those drugs whose adverse effects may somehow impair its purported benefits. Previous investigations have been carried out to ascertain the suitability of several polymers for being associated with losartan. This study is focused on the effects of Ethocel grade 10 and Carbopol 934P NF on losartan release. Flow and physical properties were assessed according to the protocols standardized by the pharmacopeia (USP-NF 29), and the drug release in phosphate buffer (pH = 6.8) was measured for 24 h. Data evidenced good to excellent flow and physical properties according to the drug/polymer ratio and the addition of co-excipients. The release rate in 24 h was found to be 63–69% to 79–82% without or with the addition of co-excipients, respectively, following zero-order kinetics. The results also suggest a significant difference with the release profile of a traditional release losartan formulation. The results suggest the suitability of Ethocel grade 10 and Carbopol 934P NF as components of a controlled-release losartan formulation.

Effect of Paclitaxel Stereochemistry on X-ray-Triggered Release of Paclitaxel from CaWO4/Paclitaxel-Coloaded PEG-PLA Nanoparticles.

For many locally advanced tumors, the chemotherapy-radiotherapy (CT-RT) combination ("chemoradiation") is currently the standard of care. Intratumoral (IT) CT-based chemoradiation has the potential to overcome the limitations of conventional systemic CT-RT (side effects). For maximizing the benefits of IT CT-RT, our laboratory has previously developed a radiation-controlled drug release formulation, in which anticancer drug paclitaxel (PTX) and radioluminescent CaWO4 (CWO) nanoparticles (NPs) are co-encapsulated with poly(ethylene glycol)-poly(lactic acid) (PEG-PLA) block copolymers ("PEG-PLA/CWO/PTX NPs"). These PEG-PLA/CWO/PTX NPs enable radiation-controlled release of PTX and are capable of producing sustained therapeutic effects lasting for at least one month following a single IT injection. The present article focuses on discussing our recent finding about the effect of the stereochemical structure of PTX on the efficacy of this PEG-PLA/CWO/PTX NP formulation. Stereochemical differences in two different PTX compounds ("PTX-S" from Samyang Biopharmaceuticals and "PTX-B" from Biotang) were characterized by 2D heteronuclear/homonuclear NMR, Raman spectroscopy, and circular dichroism measurements. The difference in PTX stereochemistry was found to significantly influence their water solubility (WS); PTX-S (WS ≈ 4.69 μg/mL) is about 19 times more water soluble than PTX-B (WS ≈ 0.25 μg/mL). The two PTX compounds showed similar cancer cell-killing performances in vitro when used as free drugs. However, the subtle stereochemical difference significantly influenced their X-ray-triggered release kinetics from the PEG-PLA/CWO/PTX NPs; the more water-soluble PTX-S was released faster than the less water-soluble PTX-B. This difference was manifested in the IT pharmacokinetics and eventually in the survival percentages of test animals (mice) treated with PEG-PLA/CWO/PTX NPs + X-rays in an in vivo human tumor xenograft study; at short times (<1 month), concurrent PEG-PLA/CWO/PTX-S NPs produced a greater tumor-suppression effect, whereas PEG-PLA/CWO/PTX-B NPs had a longer-lasting radio-sensitizing effect. This study demonstrates the importance of the stereochemistry of a drug in a therapy based on a controlled release formulation.

Evaluation of anti-arthritic activity of tofacitinib citrate controlled released formulation in complete Freund's adjuvant induced arthritis experimental model

In an animal model of complete Freund's adjuvant-induced arthritis, the tofacitinib citrate controlled-release formulation (TCRF) was examined. We examined the impact of TCRF on FCA-induced arthritis in rats, as well as weight alterations and changes in haematological and biochemical indicators. In contrast to the control group, the paw volume reduced and the animals' overall weight increased normally in the TCRF-treated animals, despite the fact that their body weight increased in the FCA-induced arthritis rats. An effective treatment for arthritis-induced haematological and biochemical abnormalities in arthritic rats was found to be TCRF at doses of 2.5, 5, 7, and 10mg/kg/p.o. At both the early and late stages of FCA-induced arthritis, the effects of treating arthritis-prone rats with TCRF showed significant reductions in rat paw edoema volume as well as a restoration of normal haematological and biochemical parameters.

Controlling drug release by introducing lipase inhibitor within a lipid formulation

Drug overdose connected to marketed pharmaceutical products, particularly opioids, occurs at an alarming rate. Novel strategies through innovative formulation approaches that reduce the likelihood of overdose while allowing safe therapeutic outcomes are urgently required. The current study provides a proof-of-concept for a new formulation approach by co-formulating drug with a lipase inhibitor within a solid lipid formulation in order to prevent or reduce the harmful effects of taking multiple doses of an oral solid dose form. Lipase inhibitor controlled-release (LICR) formulations were created using a simple hot melt method to co-formulate the inhibitor (orlistat) and ibuprofen, as the model drug, within the lipid matrix. The digestion and drug release kinetics were determined using an in vitro lipolysis model. Above a threshold level of orlistat there was decreased digestibility of multiple doses of the LICR formulations, leading to reduced drug release. Upon administration of the formulations in capsules to rats, the LICR formulation displayed the lowest exposure of ibuprofen during the pharmacokinetic studies. This novel formulation approach shows promise in preventing accidental drug overdose after oral administration of multiple doses of formulation.

Development and Evaluation of Losartan Potassium Floating Matrix Tablet

The present study was aimed towards the development of controlled release formulations of Losartan Potassium based on designed to enhance the bioavailability by prolonging its duration in the stomach via the floating dosage forms with controlled release. This study was intended to evaluate the influence of formulation variables like levels of polymer, amount of mannitol concentrations, and coating solution ratios of semi permeable membrane on the drug release from the developed formulations. Thus, there is a strong clinical need and market potential for a dosage form that will deliver Losartan Potassium in a controlled manner to a patient needing this therapy, thereby resulting in a better patient compliance. This study was designed to enhance the bioavailability of drug by prolonging its duration in the stomach via the floating dosage forms with controlled release. Floating matrix tablets of Losartan Potassium were prepared by the direct compression method, using locust bean gum and HPMC K 15M as polymers and Sodium bicarbonate as floating agent. The effect of the nature of polymers was studied by preparing various formulations of tablets. In all these formulations, a constant amount of drug (100 mg) was maintained. The blend was initially characterized for pre-compression and post- compression parameters. Pre-compression characterization was done for angle of repose, bulk density, tapped density, Carr’s index, and Hausner’s ratio. The results of pre-compression characterization were indicated good to excellent flow characteristics. Post-compression characterization includes thickness, hardness, friability, weight variation, drug content, buoyancy lag time, floating time and in-vitro drug release. All the results were satisfactory as per the guideline of pharmacopoeia. The in vitro drug release studies found that formulations LPFT4 showed best sustained release profile in 24 hrs. Among the nine formulations (LPFT1 to LPFT9) prepared formulations LPFT4 was found to be the best formulations in terms of sustained drug release. Drug release kinetics was performed by using various kinetic models such as Zero order, First order, Korsmeyer- Peppas and Higuchi’s equation and followed supercase II transport diffusion kinetic models.&#x0D; Keywords: Oral drug delivery system, Gastroretentive technology, losartan potassium, floating tablet, matrix tablet

Development of Mucoadhesive Microsphere of Quinapril Hydrochloride for Treatment of Hypertension

Mucoadhesive drug delivery systems are very widely functional approach for delivery of system within the lumen of GIT to enhance drug absorption through the part of stomach with specific manner. Quinapril hydrochloride is the hydrochloride salt of quinapril, the ethyl ester of a non-sulfhydryl, angiotensin-converting enzyme (ACE) inhibitor, quinaprilat. The quinapril hydrochloride microspheres was prepared with a coat consisting of alginate polymer i.e. sodium alginate in combination of mucoadhesive polymer chitosan/ guargum by an ionic gelation process. The microspheres were evaluated for morphological character, particle size, micromeritic properties, percentage entrapment efficiency, in-vitro wash-off test and in-vitro release studies. The drug quinapril hydrochloride was study for the release over 24 h duration. The retarding nature of system maximizing the medication discharge rate at the appropriate site within specified time period for enhancing the bioavailability of drug at desired site of action to give successful treatment to the patients experiencing hypertension The drug release of the microspheres (QLMM1 – QLMM10) was slow, extended and dependent on the composition of galactomannan concentration of polymer and stirring speed during formulation used. The mucoadhesive microspheres were adhered at intestinal pH due to highly swelling nature of composition of polymers at this pH. So, increase the adhesive strength and retarded the drug release of best composition of CH:GG in the ratio of 1:3 (QLMM6). Guargum is a highly viscous material having a property of more swelling nature due to presence of galactommannan constituent. Thus, drug release from QLMM6 was slow and extended over a period of 24 h and these microcapsules were found suitable for oral controlled release formulations.&#x0D; Keywords: Gastro-retentive drug delivery, Mucoadhesive microsphere, Quinapril hydrochloride, Pulsatile drug delivery system, Treatment of hypertension, Natural polymers