Anti-inflammatory effect of Sustained release granules of Aceclofenac in Gouty Arthritis Rat

Gout is most common painful clinical syndrome occurs due to hyperuricaemia (high serum uric acid level) and deposition of monosodium urate crystals in joints. In the current experimental study, the anti-inflammatory effect of sustained release granules of aceclofenac, was investigated on monosodium urate crystal-induced inflammation in rat. Monosodium urate is injected appropriately at a dose of 3 mg/kg body weight of a rat on right ankle to induce inflammation in joint like gouty arthritis. The percentage of joint swelling in positive control group was increased significantly (p<0.5) when compared with normal group after 1 hr, 12 hr and 24 hr with a single injection of MSU. Therapeutic effect of sustained released granules (OD) is similar to conventional released granules (BD) and possesses an anti-inflammatory effect, which could provide relief in gouty arthritis after administration of sustained release formulation of aceclofenac once in a day only. The current study clearly indicated that slow release granules of aceclofenac exerted a strong anti-inflammatory effect against gouty arthritis at standard dose once daily. It concluded that, when aceclofenac tablet is formulated with slow release granules it decreases the dosing frequency with same therapeutic effect.

Ambroxol Hydrochloride Loaded Gastro-Retentive Nanosuspension Gels Potentiate Anticancer Activity in Lung Cancer (A549) Cells

This study aimed to develop gastro-retentive sustained-release ambroxol (ABX) nanosuspensions utilizing ambroxol-kappa-carrageenan (ABX-CRGK) complexation formulations. The complex was characterized by differential scanning calorimetry, powder x-ray diffractometer, and scanning electron microscopy. The prepared co-precipitate complex was used for the development of the sustained-release formulation to overcome the high metabolic and poor solubility problems associated with ABX. Furthermore, the co-precipitate complex was formulated as a suspension in an aqueous floating gel-forming vehicle of sodium alginate with chitosan, which might be beneficial for targeting the stomach as a good absorption site for ABX. The suspension exhibited rapid floating gel behaviour for more than 8 h, thus confirming the gastro-retentive effects. Particle size analysis revealed that the optimum nanosuspension (ABX-NS) had a mean particle size of 332.3 nm. Afterward, the ABX released by the nanoparticles would be distributed to the pulmonary tissue as previously described. Based on extensive pulmonary distribution, the developed nanosuspension-released ABX nanoparticles showed significant cytotoxic enhancement compared to free ABX in A549 lung cancer cells. However, a significant loss of mitochondrial membrane potential (MMP) also occurred. The level of caspase-3 was the highest in the ABX-NS-released particle-treated samples, with a value of 416.6 ± 9.11 pg/mL. Meanwhile, the levels of nuclear factor kappa beta, interleukins 6 and 1 beta, and tumour necrosis alpha (NF-kB, IL-6, IL-1β, and TNF-α, respectively) were lower for ABX-NS compared to free ABX (p < 0.05). In caspase-3, Bax, and p53, levels significantly increased in the presence of ABX-NS compared to free ABX. Overall, ABX-NS produced an enhancement of the anticancer effects of ABX on the A549 cells, and the developed sustained-release gel was successful in providing a gastro-retentive effect.

DISCOSOMES: A FUTURISTIC UPHEAVAL IN VESICULAR DRUG DELIVERY

The formulation system employed to convey pharmaceutical drugs compound in the body to attain the desired therapeutic effect at a predetermined rate depending on pharmacological aspects, drug profile, and physiological conditions can be referred to as a novel drug delivery system (NDDS). Due to the intricately sensitive anatomy and physiology of the eye pharmacologist find the ocular delivery system to be more involuted than other routes. Pre-corneal, static and dynamic is the 3 types of ophthalmic barriers, which along with the inflow and outflow of lacrimal fluids, nasolacrimal drainage, are some of the germane factors that affect bioavailability. Unlike conventional dosage forms, where the distribution of drugs in non-targeted body fluids and tissues transcends the quantity of required drug in targeted tissues and causes repercussions, these modified drug delivery systems surpass the ocular barriers and adverse reactions, emphasizing on less invasive, prolonged action. It also promotes sustained release formulation that subjugates the drug loss or degradation to treat many ocular diseases effectively. The current review recapitulates the fundamentals of discosomes, a type of vesicular drug delivery system that acts as a vehicle for the drug delivery of both hydrophilic and lipophilic drugs. Discosomes are giant, disc-shaped structures modified from niosomes by arresting the vesicles at the discosome phase. Due to their idiosyncratic size, it provides all due benefits compared to other ocular drug delivery systems. From the review, it can be culminated that discosomes are a potential subject of opposition and opportunities in the arena of safe and effective ocular drug delivery.

An in vivo pharmacokinetic study of metformin microparticles as an oral sustained release formulation in rabbits

Background Metformin hydrochloride is a biguanide derivative that has been widely used to treat type 2 diabetes in humans. In veterinary medicine, metformin has shown increasing potential for diabetes treatment in different species, such as equids, dogs, cats and rabbits. It is highly hydrophilic, with incomplete gastrointestinal absorption and very large variability in absolute bioavailability between species, ranging from 4% in equids to 60% in humans. Metformin also shows a short half-life of approximately 2 h in dogs, cats, horses and humans. The objectives of this study were to evaluate a poly (lactic acid) (PLA) metformin microparticle formulation to test in rabbits and conduct a pharmacokinetics study of intravenous (SIV) and oral solution (SPO) metformin administration and oral PLA microparticle (SPLA) administration to rabbits to evaluate the improvement in the metformin pharmacokinetics profile. Results Metformin-loaded PLA microparticles were characterized by a spherical shape and high encapsulation efficiency. The results from Fourier transform infrared (FTIR) spectroscopy suggested the presence of interactions between metformin and PLA. X-Ray diffraction (XRD) analysis corroborated the results from the differential scanning calorimetry (DSC) studies, showing that metformin is present in an amorphous state within the microparticles. Physicochemical characterization suggested that PLA and metformin hydrochloride interacted within the microparticles via hydrogen bonding interactions. The pharmacokinetic study in rabbits showed sustained-release characteristics from the prepared microparticles with a delay in the time needed to reach the maximum concentration (Tmax), decreased Cmax and bioavailability, and increased mean residence time (MRT) and half-life compared to the pure drug solution. Conclusions Metformin-loaded PLA microparticles showed optimal and beneficial properties in terms of their physicochemical characteristics, making them suitable for use in an in vivo pharmacokinetic study. The pharmacokinetic parameters of the metformin microparticles from the in vivo study showed a shorter Tmax, longer MRT and half-life, decreased Cmax and the prolonged/sustained release expected for metformin. However, the unexpected decrease in bioavailability of metformin from the microparticles with respect to the oral solution should be evaluated for microparticle and dose design in future works, especially before being tested in other animal species in veterinary medicine.

FORMULATION AND EVALUATION OF METFORMIN HYDROCHLORIDE AND GLICLAZIDE SUSTAINED RELEASE BILAYER TABLETS: A COMBINATION THERAPY IN MANAGEMENT OF DIABETES

Objective: The main objective of the present investigation is to develop a sustained-release (SR) formulation to optimize the postprandial elevation of glucose level in type 2 Diabetic subjects using combination therapy. In the present research work, bilayer sustained release formulation of metformin hydrochloride (MFH) and gliclazide (GLZ), based on monolithic-matrix technology was developed and evaluated. Methods: The formulations of metformin hydrochloride layer and gliclazide layer that contain polyox WSR coagulant and different viscosity grades of hydroxyl propyl methylcellulose (HPMC) as sustained-release matrix were prepared by direct compression and wet granulation method respectively. The bilayer tablets were prepared after carrying out the optimization of metformin layer and evaluated for various pre-compression and post-compression parameters. For the best formulation selected on basis of in vitro evaluation of tablets, Fourier-transform infrared spectroscopy (FT-IR) studies and comparison of in vitro dissolution profile of developed formulation with the innovator were performed. Results: Metformin hydrochloride and gliclazide showed sustained release of drug by diffusion mechanism and followed first-order kinetics. The best formulation of metformin hydrochloride (M7) and gliclazide (G8) show 99.93% and 99.65% of drug release in 24 h respectively. The similarity factor (f2) was 79.95 for metformin hydrochloride and 73.62 for gliclazide when compared with the innovator. Conclusion: The monolith diffusion-controlled bilayer tablets of metformin hydrochloride and gliclazide offer improved patient compliance and convenience with better postprandial hyperglycemic control with once-a-day dosing. The sustained release of the drug up to 24 h regulate antidiabetic activity round the clock with minimal side effects.

Preliminary Investigation into a Novel Sustained-Release Formulation of Meloxicam in Sheep (Ovis aries)—Pharmacokinetic Profile

This study is a preliminary investigation describing the pharmacokinetic profile of a novel subcutaneous sustained-release meloxicam formulation (SRMF) in sheep. Six merino ewe hoggets (41.5 ± 4.6 kg) were treated with a novel subcutaneous SRMF at 2 mg/kg bodyweight (BW). Blood samples were collected at t = 0, 2, 4, 6, 8, 10, 12, 24, 48, 96, 144, 168, 192, and 336 h following treatment, and interstitial (ISF) fluid samples were collected at periods of 8 to 12 h, 12 to 24 h, 24 to 48 h, 48 to 52 h, and 92 to 96 h following treatment. High-pressure liquid chromatography (HPLC) analysis with ultraviolet detection was utilised to determine the concentration of meloxicam in plasma and ISF. The SRMF exhibited the following mean (±SD) pharmacokinetic indices: Cmax of 1.58 μg/mL (±0.82 μg/mL) at a Tmax of 10.0 h (±1.79 h), and half life (t1/2) of 31.4 h (±13.17 h) in sheep plasma. Interstitial fluid samples were collected from three of the six sheep, with a decrease in meloxicam concentration exhibited over 52 h. This study demonstrates a variable extended t1/2, a delayed Tmax, and a lower Cmax of the SRMF, as compared to that of a conventional meloxicam formulation (CMF) in sheep, as previously referenced (t1/2: 14.28 h; Tmax: 5 h; Cmax: 15.94 μg/mL). Further research to determine the clinical efficacy and safety of the SRMF in sheep is warranted.

Liqui-Mass Technology as a Novel Tool to Produce Sustained Release Liqui-Tablet Made from Liqui-Pellets

The Liqui-Mass technology (also known as Liqui-Pellet technology) has shown promising results in terms of enhancing the drug release rate of water insoluble drugs in a simplistic approach. However, there is no current study on sustained-release formulation using the Liqui-Mass technology. In this study, an attempt was made to produce a sustained-release Liqui-Tablet for the first time using a matrix-based approach. The non-volatile co-solvent used in the investigation included Tween 80, Tween 20 and Kolliphor EL. The production of sustained-release propranolol hydrochloride Liqui-Tablet was successful, and data from the saturation solubility test and dissolution test did not show much difference among the mentioned non-volatile co-solvent. The best Liqui-Tablet formulation took 24 h for drug release to reach at around 100%. There seemed to be a synergistic retarding drug release effect when a non-volatile co-solvent and Eudragit RS PO were used together. The increase of Eudragit RS PO concentration increased the retardant effect. Kinetic drug release analysis suggests that the best formulation followed the Higuchi model. The flowability of pre-compressed Liqui-Tablet pellets had no issues and its size distribution was narrow. Liqui-Tablet was generally robust and most formulations passed the friability test. The study revealed that Liqui-Mass technology can be employed to sustain drug release.

The impacts of PLGA/PEG triblock copolymers with variable molecular weights on sustained release of buprenorphine

Introduction: Current in-situ injectable implants of buprenorphine (BP) such as Sublocade® consist of N-methyl-2-pyrrolidone (NMP)-dissolved PLGA. To control the initial burst release of Sublocade® during the first 24 hours after injection, we used a BP in-situ forming composite (ISFC) to employ different molecular weights of PLGA-PEG-PLGA triblock. Methods: The triblock was synthesized by ring-opening polymerization (ROP) using PEG molecules with weights of 1500, 3000, and 4000 Da via the melting method. The specifications of the triblock were evaluated by 1H-NMR, FTIR, GPC, and DSC. The sol-gel, gel-precipitate temperatures, in-vitro release, and composites’ morphology, degradation, and toxicity were assessed for determining the features of ISFC 1500, ISFC 3000, and ISFC 4000 formulations. ROP was performed successfully via the melting method. The yields of all polymerization reactions were greater than 83.4 %. Results: The PEG 1500 triblock showed both sol-gel and gel-precipitate temperatures, but PEG 3000 and 4000 only showed a sol-precipitate temperature. The values of initial burst release of BP from ISFC 1500, ISFC 3000, and ISFC 4000 were 6.52 ± 0.22 %, 12.39 ± 0.61 %, and 15.80 ± 0.98 %, respectively. BP release from the ISFCs was completed over three weeks for ISFC 1500 and 10 days for ISFC 3000 and ISFC 4000. The composites containing PEG 3000 and PEG 4000 were more spongy and porous than PEG 1500. The ISFC 1500 delivered a higher cell viability (95.17 ± 1.15 %) compared with ISFC 3000 (86.37 ± 2.25%) and ISFC 4000 (79.70 ± 3.77%). Conclusion: These results indicated that ISFC 1500 were biocompatible and delivered suitable early initial burst reactions compared with ISFC 3000 and 4000 and might be a good candidate for preparing sustained-release formulation of BP.