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ABSTRACT Levetiracetam (LEV) is an anti‐epileptic drug used extra‐label in dogs. Commercially available extended‐release formulations (LEV‐ER), administered twice daily, cannot be crushed or split, limiting their use in small dogs. A compounded LEV‐ER formulation (PO‐COMP) can purportedly be partitioned without loss of extended‐release properties. The aims of this study were to establish the pharmacokinetic parameters of PO‐COMP, divided at the tablet score, and determine the bioequivalence of partitioned PO‐COMP to an intact commercially available Food and Drug Administration‐approved human oral generic formulation of LEV‐ER (PO‐COMM). In a randomized crossover design, 12 healthy dogs received a single IV dose (30 mg/kg) of IV‐COMM, a single oral dose (500 mg) of intact PO‐COMM, or a single oral dose (500 mg) of partitioned PO‐COMP and underwent serial measurement of plasma LEV concentrations over 24 h. PO‐COMP was bioequivalent to PO‐COMM using the 90% confidence interval method for maximum concentration (−3.2% difference [CI −7.4% to −1.1%]) and area under the curve (−14.4% difference [CI −17.8% to 10.8%]). PO‐COMP may improve medication adherence and seizure control relative to immediate‐release LEV, which requires three times daily dosing. Efficacy studies of PO‐COMP are warranted. [ABSTRACT FROM AUTHOR]

This study outlines the development of a cost-effective, extended-release febuxostat (FEB) tablet using activated charcoal as an adsorbent to enhance drug release. FEB, a BCS Class II drug, presents formulation challenges due to low solubility and high lipophilicity. We evaluated eight formulations with varying FEB-to-charcoal ratios using FTIR and DSC for physical interactions and followed USP standards for overall assessment. The optimal 1:0.25 FEB-to-charcoal ratio demonstrated a consistent 12 h zero-order release pattern. In vivo studies indicated a significantly extended plasma profile compared to immediate-release tablets. The optimal tablets demonstrated acceptable hardness and disintegration times. This innovative approach enhances patient compliance, improves bioavailability, and reduces production costs, offering a promising solution for controlled FEB delivery. [ABSTRACT FROM AUTHOR]

Hydrogels are extensively employed in healthcare due to their adaptable structures, high water content, and biocompatibility, with FDA‐approved applications ranging from spinal cord regeneration to local therapeutic delivery. However, clinical hydrogels encounter challenges related to inconsistent therapeutic exposure, unmodifiable release windows, and difficulties in subsurface polymer insertion. Addressing these issues, we engineered injectable, biocompatible hydrogels as a local therapeutic depot, utilizing poly(ethylene glycol) (PEG)‐based hydrogels functionalized with bioorthogonal SPAAC handles for network polymerization and functionalization. Our hydrogel solutions polymerize in situ in a temperature‐sensitive manner, persist in tissue, and facilitate the delivery of bioactive therapeutics in subsurface locations. Demonstrating the efficacy of our approach, recombinant anti‐CD47 monoclonal antibodies, when incorporated into subsurface‐injected hydrogel solutions, exhibited cytotoxic activity against infiltrative high‐grade glioma xenografts in the rodent brain. To enhance the gel's versatility, recombinant protein cargos can undergo site‐specific modification with hydrolysable "azidoester" adapters, allowing for user‐defined release profiles from the hydrogel. Hydrogel‐generated gradients of murine CXCL10, linked to intratumorally injected hydrogel solutions via azidoester linkers, resulted in significant recruitment of CD8+ T‐cells and the attenuation of tumor growth in a "cold" syngeneic melanoma model. This study highlights a highly customizable, hydrogel‐based delivery system for local protein therapeutic administration to meet diverse clinical needs. [ABSTRACT FROM AUTHOR]

Effective treatment of postoperative pain lasting for multiple days without opioids is an important clinical need. We previously reported analgesia lasting up to 96 h in a porcine soft tissue model of postoperative pain using SBG004, an extended-release formulation of bupivacaine based on the temperature-responsive polymer poly(N-isopropylacrylamide-co-dimethylbutyrolactone acrylamide-co-Jeffamine M-1000 acrylamide) [PNDJ]. Orthopaedic surgical sites such as the knee can involve complex sensory innervation which presents a distinct challenge to local anesthetic delivery. The purpose of this work was to evaluate the pharmacokinetics and efficacy of SBG004 in an orthopaedic surgical model in comparison to currently available local anesthetics. Pharmacokinetics following periarticular (PA) or intraarticular (IA) injection of SBG004 were compared against liposomal bupivacaine (Lip-Bupi) PA in New Zealand White rabbits (all doses 14.5 mg/kg). Analgesic efficacy of SBG004 (IA, PA, or IA + PA), three active comparators, and saline was evaluated following knee surgery in New Zealand White rabbits. Analgesia was assessed via weight-bearing on the operated limb during spontaneous large steps in video recordings. Systemic bupivacaine exposure lasted at least 7 days for SBG004 PA, 4 days for SBG004 IA, and 2 days for Lip-Bupi PA. In the analgesia study, weight-bearing in all active groups except SBG004 IA was more frequent versus saline through 8 h postoperatively (p < 0.05). Only SBG004 IA + PA resulted in a higher proportion of weight-bearing rabbits at 24 h versus saline (6/7 versus 2/10, p = 0.015). Analysis of pooled data from 24–72 h showed significantly greater frequency of weight-bearing in rabbits receiving SBG004 IA + PA (71%) versus saline (37%), ropivacaine cocktail (41%), and Lip-Bupi PA (36%). The results indicate that the release profile from SBG004 PA or IA coincides reasonably with the time course of postoperative pain, and SBG004 may produce longer duration of analgesia than local anesthetics currently used in knee surgery, including during the period of 24–72 h recognized as a target for extended-release local anesthetics. [ABSTRACT FROM AUTHOR]

Background: In the REST-ON clinical trial (NCT02720744), mean sleep latency on the Maintenance of Wakefulness Test (MWT) was significantly improved with extended-release once-nightly sodium oxybate (ON-SXB) vs placebo (P 10 % remained awake for the entirety of the MWT. ON-SXB offers a once-at-bedtime treatment option for adults with narcolepsy.

Lynn Webster,1 Jeffrey Gudin2 1Dr. Vince Clinical Research, Overland Park, KS, USA; 2Department of Anesthesiology and Pain Management, University of Miami, Miller School of Medicine, Miami, FL, USACorrespondence: Lynn Webster, Dr. Vince Clinical Research, 1285 3rd Avenue, Salt Lake City, UT, 84103, USA, Tel +1 801-560-1707, Email LRWebsterMD@gmail.comAbstract: The misuse and abuse of opioid analgesics continue to pose a serious public health concern, but for some patients, opioids remain an important analgesic option. Extended-release (ER) opioid formulations are effective for treating chronic pain and are supported by multiple 12-week efficacy studies. ER opioids often contain a high opioid content, and similar to immediate-release (IR) formulations, are subject to abuse, misuse, and diversion. Unintentional misuse may also occur when ER formulations are manipulated for medicinal administration, such as crushing a dose for easier oral intake. As part of a multipronged strategy designed to fight the opioid epidemic, abuse-deterrent formulations (ADFs) were developed to deter misuse, abuse, and diversion of opioids by making manipulation more difficult and nonoral routes of administration less rewarding. Although ADF opioids have been shown to decrease rates of abuse and diversion, they are not equally effective in terms of deterring manipulation for abuse or misuse. Xtampza ER utilizes DETERx technology, which allows it to retain ER characteristics when chewed or crushed, making it the only ER opioid without a boxed warning against these types of manipulation. OxyContin was also developed as an ADF but uses RESISTEC technology, making the tablet hard to crush and viscous in aqueous solutions. ADF utilization has been hampered by patient access issues, including high prices due to lack of insurance coverage. Postmarket real-world studies demonstrate lower rates of abuse, misuse, and diversion for ADF ER opioids compared with non-ADF formulations. However, similar studies comparing abuse-related effectiveness and health care costs for ADF opioids are warranted if clinicians are expected to utilize these potentially safer opioid formulations. These studies would support further education surrounding the benefits and utilization of ADFs and manipulation potential of different ADFs.Keywords: opioid analgesics, opioid crisis, chronic pain, tamper, abuse-deterrent, extended release

The mathematical models available in DDSolver were applied to experimental dissolution data obtained by analysing carvedilol release from hypromellose (HPMC)-based matrix tablets. Different carvedilol release profiles were generated by varying a comprehensive selection of fillers and carvedilol release modifiers in the formulation. Model fitting was conducted for the entire relevant dissolution data, as determined by using a paired t-test, and independently for dissolution data up to approximately 60% of carvedilol released. The best models were selected based on the residual sum of squares (RSS) results used as a general measure of goodness of fit, along with the utilization of various criteria for visual assessment of model fit and determination of the acceptability of estimated model parameters indicating burst release or lag time concerning experimental dissolution results and previous research. In addition, a model-dependent analysis of carvedilol release mechanisms was carried out. [ABSTRACT FROM AUTHOR]

Abstract Hydrogels are extensively employed in healthcare due to their adaptable structures, high water content, and biocompatibility, with FDA‐approved applications ranging from spinal cord regeneration to local therapeutic delivery. However, clinical hydrogels encounter challenges related to inconsistent therapeutic exposure, unmodifiable release windows, and difficulties in subsurface polymer insertion. Addressing these issues, we engineered injectable, biocompatible hydrogels as a local therapeutic depot, utilizing poly(ethylene glycol) (PEG)‐based hydrogels functionalized with bioorthogonal SPAAC handles for network polymerization and functionalization. Our hydrogel solutions polymerize in situ in a temperature‐sensitive manner, persist in tissue, and facilitate the delivery of bioactive therapeutics in subsurface locations. Demonstrating the efficacy of our approach, recombinant anti‐CD47 monoclonal antibodies, when incorporated into subsurface‐injected hydrogel solutions, exhibited cytotoxic activity against infiltrative high‐grade glioma xenografts in the rodent brain. To enhance the gel's versatility, recombinant protein cargos can undergo site‐specific modification with hydrolysable “azidoester” adapters, allowing for user‐defined release profiles from the hydrogel. Hydrogel‐generated gradients of murine CXCL10, linked to intratumorally injected hydrogel solutions via azidoester linkers, resulted in significant recruitment of CD8+ T‐cells and the attenuation of tumor growth in a “cold” syngeneic melanoma model. This study highlights a highly customizable, hydrogel‐based delivery system for local protein therapeutic administration to meet diverse clinical needs.

In this study, a novel floating, controlled-release and core-shell oral tablet of ketamine hydrochloride (HCl) was produced using a dual extrusion by 3D printing method. A mixture of Soluplus® and Eudragit® RS-PO was extruded by a hot-melt extrusion (HME) nozzle at 150–160 °C to fabricate the tablet shell, while a second nozzle known as a pressure-assisted syringe (PAS) extruded the etamine HCl in carboxymethyl cellulose gel at room temperature (25 °C) inside the shell. The resulting tablets were optimized based on the United States pharmacopeia standards (USP) for solid dosage forms. Moreover, the tablet was characterized using Fourier-transform infrared (FTIR) spectrum, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and buoyancy techniques. The results showed a desired dissolution profile for a 100% infill optimized tablet with total drug release (100%) during 12 h. Weight variation and content uniformity of the tablets achieved the USP requirements. SEM micrographs showed a smooth surface with acceptable layer diameters. According to the FTIR analysis, no interference was detected among peaks. Based on DSC analysis, the crystallinity of ketamine HCl did not change during melt extrusion. In conclusion, the floating controlled-release 3D-printed tablet of ketamine HCl can be a promising candidate for management of refractory depressions and chronic pain. Additionally, the additive manufacturing method enables the production of patient-tailored dosage with tunable-release kinetics for personalized medicine in point-of care setting. [ABSTRACT FROM AUTHOR]

Background: IPX203 is a novel oral extended‐release formulation of carbidopa/levodopa (CD/LD) developed to address the short half‐life of immediate‐release CD/LD. In the phase 3 RISE‐PD trial, IPX203 significantly improved "Good On" time in patients with Parkinson's disease compared with immediate‐release CD/LD. Objectives: To evaluate the safety and efficacy of IPX203 in an open‐label extension of the pivotal phase 3 study. Methods: This 9‐month extension enrolled patients who completed the randomized, double‐blind trial. Key efficacy endpoints included Movement Disorder Society‐Unified Parkinson's Disease Rating Scale and Patient and Clinical Global Impression scores. Adverse events (AEs) were recorded. Results: Improvements in efficacy were maintained and dosing frequency and total daily dose remained stable through the trial. A total of 52.7% of patients experienced ≥1 treatment‐emergent AE, mostly mild or moderate and occurred within the first 90 days of treatment. Conclusions: In this phase 3 open‐label extension, IPX203 exhibited a favorable safety and tolerability profile and sustained efficacy of comparable magnitude to the end of the double‐blind study. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Purpose: The study aims to develop an interpenetrating polymer network (IPN) hydrogel bead. This drug carrier system with a hydrophilic polymer is designed through an ionotropic gelation technique using divalent calcium ions as a crosslinking agent. The resultant polymeric composite extends the release of the short-acting oral sulfonylurea drug, glipizide. Methods: The IPN hydrogel beads prepared with more than one polymer bring forth better mechanical strength in contrast to a single polymeric-based network hydrogel system. This hydrogel bead of hydrophilic sodium alginate (SAL), the concentration of which ranges from 1.5 to 2.0% w/w, and xanthan gum (XAG) polymer, whose concentration ranges between 0.5 and 1.0% w/w, has been prepared to control the drug release profile. An ionotropic gelation technique with the crosslinking agent, calcium chloride at 2.5–7.5% w/w concentration, was adopted to prepare the IPN hydrogel bead drug carrier. Results: The prepared hydrogel bead was studied for viscosity analysis of prepared composite dispersion, particle size, drug entrapment, swelling functions, and in vitro drug dissolution. An increase in xanthan gum quantity levels resulted in increased viscosity of prepared composite dispersions and hence the increased mean diameter of produced IPN hydrogel beads. Increased crosslinker concentration showed a slightly smaller IPN hydrogel bead mean diameter and increased encapsulation of loaded drug to about 88 to 91% glipizide. The in vitro drug dissolution was observed to be slower with increased xanthan gum polymer and calcium ion crosslinker concentration, which extended the drug release to 14 h. Thus, this work demonstrates that the XAG and calcium ion crosslinkers play a significant role in controlling the release of the loaded drug, glipizide. Conclusion: Based on the results obtained, it can be concluded that the prepared novel polymeric-based IPN drug carrier system has beneficially controlled the drug release of short-acting oral sulphonyl medication and acted as an extended drug release system. [ABSTRACT FROM AUTHOR]

This study outlines the development of a cost-effective, extended-release febuxostat (FEB) tablet using activated charcoal as an adsorbent to enhance drug release. FEB, a BCS Class II drug, presents formulation challenges due to low solubility and high lipophilicity. We evaluated eight formulations with varying FEB-to-charcoal ratios using FTIR and DSC for physical interactions and followed USP standards for overall assessment. The optimal 1:0.25 FEB-to-charcoal ratio demonstrated a consistent 12 h zero-order release pattern. In vivo studies indicated a significantly extended plasma profile compared to immediate-release tablets. The optimal tablets demonstrated acceptable hardness and disintegration times. This innovative approach enhances patient compliance, improves bioavailability, and reduces production costs, offering a promising solution for controlled FEB delivery.

Effective treatment of postoperative pain lasting for multiple days without opioids is an important clinical need. We previously reported analgesia lasting up to 96 h in a porcine soft tissue model of postoperative pain using SBG004, an extended-release formulation of bupivacaine based on the temperature-responsive polymer poly(N-isopropylacrylamide-co-dimethylbutyrolactone acrylamide-co-Jeffamine M-1000 acrylamide) [PNDJ]. Orthopaedic surgical sites such as the knee can involve complex sensory innervation which presents a distinct challenge to local anesthetic delivery. The purpose of this work was to evaluate the pharmacokinetics and efficacy of SBG004 in an orthopaedic surgical model in comparison to currently available local anesthetics. Pharmacokinetics following periarticular (PA) or intraarticular (IA) injection of SBG004 were compared against liposomal bupivacaine (Lip-Bupi) PA in New Zealand White rabbits (all doses 14.5 mg/kg). Analgesic efficacy of SBG004 (IA, PA, or IA + PA), three active comparators, and saline was evaluated following knee surgery in New Zealand White rabbits. Analgesia was assessed via weight-bearing on the operated limb during spontaneous large steps in video recordings. Systemic bupivacaine exposure lasted at least 7 days for SBG004 PA, 4 days for SBG004 IA, and 2 days for Lip-Bupi PA. In the analgesia study, weight-bearing in all active groups except SBG004 IA was more frequent versus saline through 8 h postoperatively (p < 0.05). Only SBG004 IA + PA resulted in a higher proportion of weight-bearing rabbits at 24 h versus saline (6/7 versus 2/10, p = 0.015). Analysis of pooled data from 24–72 h showed significantly greater frequency of weight-bearing in rabbits receiving SBG004 IA + PA (71%) versus saline (37%), ropivacaine cocktail (41%), and Lip-Bupi PA (36%). The results indicate that the release profile from SBG004 PA or IA coincides reasonably with the time course of postoperative pain, and SBG004 may produce longer duration of analgesia than local anesthetics currently used in knee surgery, including during the period of 24–72 h recognized as a target for extended-release local anesthetics.

The poor aqueous solubility is a well-recognized restriction for the clinical application of many drug molecules. Micelles delivery system provides a promising strategy for the solubility enhancement of hydrophobic drugs. This study developed and evaluated different polymeric mixed micelles prepared using hot-melt extrusion coupled hydration method to improve the solubility and extend the release of the model drug ibuprofen (IBP). The physicochemical properties of the prepared formulations were characterized in terms of particle size, polydispersity index, zeta potential, surface morphology, crystallinity, encapsulation efficiency, drug content, in vitro drug release, dilution stability, and storage stability. Soluplus®/poloxamer 407, Soluplus®/poloxamer 188, and Soluplus®/TPGS mixed micelles had average particle sizes of 86.2 ± 2.8, 89.6 ± 4.2, and 102.5 ± 3.13 nm, respectively with adequate encapsulation efficiencies of 80% to 92%. Differential scanning calorimetry studies confirmed that the IBP molecules were dissolved in the polymers in an amorphous state. The in vitro release results revealed that the IBP-loaded mixed micelles presented extended-release behavior compared to the free drug. In addition, the developed polymeric mixed micelles remained stable upon dilution and one-month storage. These results demonstrated that the hot-melt extrusion coupling hydration method could be a promising, effective, and environment-friendly manufacturing technique for the scale-up production of polymeric mixed micelles to deliver insoluble drugs. [Display omitted] [ABSTRACT FROM AUTHOR]

The mathematical models available in DDSolver were applied to experimental dissolution data obtained by analysing carvedilol release from hypromellose (HPMC)-based matrix tablets. Different carvedilol release profiles were generated by varying a comprehensive selection of fillers and carvedilol release modifiers in the formulation. Model fitting was conducted for the entire relevant dissolution data, as determined by using a paired t-test, and independently for dissolution data up to approximately 60% of carvedilol released. The best models were selected based on the residual sum of squares (RSS) results used as a general measure of goodness of fit, along with the utilization of various criteria for visual assessment of model fit and determination of the acceptability of estimated model parameters indicating burst release or lag time concerning experimental dissolution results and previous research. In addition, a model-dependent analysis of carvedilol release mechanisms was carried out.

An extended-release tablet of tacrolimus as once-daily dosing was fabricated using 3D printing technology. It was developed by combining two 3D-printing methods in parallel. Indeed, an optimized mixture of PVA, sorbitol, and magnesium stearate as a shell compartment was printed through a hot-melt extrusion (HME) nozzle while an HPMC gel mixture of the drug in the core compartment was printed by a pressure-assisted micro-syringe (PAM). A 3D-printed tablet with an infill of 90% was selected as an optimized formula upon the desired dissolution profile, releasing 86% of the drug at 12 h, similar to the commercial one. The weight variation, friability, hardness, assay, and content uniformity determination met USP requirements. A microbial evaluation showed that the 3D-printed tablet does not support microbial growth. SEM analysis showed smooth surfaces with multiple deposited layers. No peak interference appeared based on FTIR analysis. No decomposition of the polymer and drug was observed in the printing temperature, and no change in tacrolimus crystallinity was detected based on TGA and DSC analyses, respectively. The novel, sTable 3D-printed tablet, fabricated using controllable additive manufacturing, can quickly provide tailored dosing with specific kinetic release for personalized medicine at the point-of-care. [ABSTRACT FROM AUTHOR]

Regulated delivery of drugs plays a key role in control and treatment of diabetes type II. The lack of patient compliance is one of the main hurdles of successful regulated drug delivery. Extended release drug delivery systems are one of the best solutions for this problem. Electrospinning is an easy method for production of nanofibers as drug delivery systems capable of being tailored for various release kinetics, including extended release form. Response surface methodology is employed to fine tune input variables, including electrical field intensity, base polymer ratio, and total polymer concentration to study the behavior of output parameters. The study validates the feasibility of using polyethylene glycol (PEG)/polycaprolctone (PCL) nanofibers drug delivery systems as an extended time release medium for metformin and glibenclamide co-delivery. A new drug release model is presented and its parameters indicate the possibility of using drug for at least T 60 = 60 h with average and sustained release rate of 5.37 μ g drug / g solid h . The system traps as little as 10% of loaded metformin and 23% of loaded glibenclamide. The mathematical model presented in this study can be used to predict the release behavior of various drug release systems. Because it can account for the varying beginning slope of the release profile, it is capable of correctly assessing the release behavior of slow release to burst release drug delivery systems. The degree of swelling and weight loss (2.48 ± 0.26% and 0.44 ± 0.02%) of prepared samples and the effect of slightly acidic pH was investigated showed that these formulations could be considered for trans dermal delivery of metformin and glibenclamide. In-vitro study of L6 myotube cells also indicated that the delivery system is capable of retaining acceptable glucose intake at 72 and 168 h (65.95 ± 4.59 % and 45.17 ± 5.12 % respectively). [ABSTRACT FROM AUTHOR]

Acne is a common skin condition caused by the growth of certain bacteria. Many plant extracts have been investigated for their potential to combat acne-inducing microbes, and one such plant extract is microwave-assisted Opuntia humifusa extract (MA-OHE). The MA-OHE was loaded onto zinc-aminoclay (ZnAC) and encapsulated in a Pickering emulsion system (MA-OHE/ZnAC PE) to evaluate its therapeutic potential against acne-inducing microbes. Dynamic light scattering and scanning electron microscopy were used to characterize MA-OHE/ZnAC PE with a mean particle diameter of 353.97 nm and a PDI of 0.629. The antimicrobial effect of MA-OHE/ZnAC was evaluated against Staphylococcus aureus (S. aureus) and Cutibacterium acnes (C. acnes), which contribute to acne inflammation. The antibacterial activity of MA-OHE/ZnAC was 0.1 and 0.025 mg/mL to S. aureus and C. acnes, respectively, which were close to naturally derived antibiotics. Additionally, the cytotoxicity of MA-OHE, ZnAC, and MA-OHE/ZnAC was tested, and the results showed that they had no cytotoxic effects on cultured human keratinocytes in a range of 10–100 μg/mL. Thus, MA-OHE/ZnAC is suggested to be a promising antimicrobial agent for treating acne-inducing microbes, while MA-OHE/ZnAC PE is a potentially advantageous dermal delivery system. [ABSTRACT FROM AUTHOR]

Simple Summary: Pharmacokinetic (PK) studies measure the time for a dose of a drug to reach therapeutic levels in a patient's blood or tissues. This data provides a simple and precise method to compare the response to drugs made by different manufactures or the same drug provided in different delivery formats; for example, oral tablets, intravenous infusions, or subcutaneous (SC) injections. The present study provides the first review of PK data for buprenorphine, an opioid analgesic, in animals dosed with the drug in a lipid or polymer carrier. The PK data from studies using the polymer carrier system illustrate greater variability, an outcome probably related to the different manufacturing conditions of the supplying vendors. The lipid product was produced by a single vendor. Long-acting injectable (LAI) opioid formulations mitigate the harm profiles and management challenges associated with providing effective analgesia for animals. A single dose of a long-acting opioid analgesic can provide up to 72 h of clinically relevant pain management. Yet, few of these new drugs have been translated to products for veterinary clinics. Regulatory pathways allow accelerated drug approvals for generic and biosimilar drugs. These pathways depend on rigorous evidence for drug safety and pharmacokinetic evidence demonstrating bioequivalence between the new and the legacy drug. This report reviews the animal PK data associated with lipid and polymer-bound buprenorphine LAI formulations. Buprenorphine is a widely used veterinary opioid analgesic. Because of its safety profile and regulatory status, buprenorphine is more accessible than morphine, methadone, and fentanyl. This review of PK studies coupled with the well-established safety profile of buprenorphine suggests that the accelerated approval pathways may be available for this new family of LAI veterinary pharmaceuticals. [ABSTRACT FROM AUTHOR]

[Display omitted] Colon absorption is a key determinant for successful development of extended release and colon targeted drug products. This is the first systematic evaluation of the ability to predict in vivo regional differences in absorption and the extent of colon absorption in humans using mechanistic physiologically based biopharmaceutics modeling (PBBM). A new dataset, consisting of 19 drugs with a wide range of biopharmaceutics properties and extent of colon absorption in humans, was established. Mechanistic predictions of the extent of absorption and plasma exposure after oral, or jejunal and direct colon administration were performed in GastroPlus and GI-Sim using an a priori approach. Two new colon models developed in GI-Sim, were also evaluated to assess if the prediction performance could be improved. Both GastroPlus and GI-Sim met the pre-defined criteria for accurate predictions of regional and colon absorption for high permeability drugs irrespective of formulation type, while the prediction performance was poor for low permeability drugs. For solutions, the two new GI-Sim colon models improved the colon absorption prediction performance for the low permeability drugs while maintaining the accurate prediction performance for the high permeability drugs. In contrast, the prediction performance decreased for non-solutions using the two new colon models. In conclusion, PBBM can be used with sufficient accuracy to predict regional and colon absorption in humans for high permeability drugs in candidate selection as well as early design and development of extended release or colon targeted drug products. The prediction performance of the current models needs to be improved to allow high accuracy predictions for commercial drug product applications including highly accurate predictions of the entire plasma concentration–time profiles as well as for low permeability drugs. [ABSTRACT FROM AUTHOR]

Solid dosage forms based on hypromellose (HPMC) with prolonged/extended drug release are very important from the research and industrial viewpoint. In the present research, the influence of selected excipients on carvedilol release performance from HPMC-based matrix tablets was studied. A comprehensive group of selected excipients was used within the same experimental setup, including different grades of excipients. Compression mixtures were directly compressed using constant compression speed and main compression force. LOESS modelling was used for a detailed comparison of carvedilol release profiles via estimating burst release, lag time, and times at which a certain % of carvedilol was released from the tablets. The overall similarity between obtained carvedilol release profiles was estimated using the bootstrapped similarity factor (f2). In the group of water-soluble carvedilol release modifying excipients, which produced relatively fast carvedilol release profiles, POLYOXᵀᴹ WSR N-80 and Polyglykol® 8000 P demonstrated the best carvedilol release control, and in the group of water-insoluble carvedilol release modifying excipients, which produced relatively slow carvedilol release profiles, AVICEL® PH-102 and AVICEL® PH-200 performed best. [ABSTRACT FROM AUTHOR]

Introduction: Lithium carbonate is used in the treatment of bipolar affective disorder; however, it requires strict control of serum levels because it is one of the drugs for psychiatric use with a narrow therapeutic margin. Extended-release lithium carbonate formulations have the advantage of providing more consistent serum concentrations, leading to fewer adverse events and better adherence to treatment. Aim: To manufacture and optimize through a factorial design of experiments a lithium carbonate matrix system with a low viscosity HPMC (Methocel® E15LV), to obtain tablets that meet the extended-release criteria of the Pharmacopoeia of the United Mexican States (FEUM). Methods: The tablets were manufactured by wet granulation and characterized by pharmacopeial tests including in vitro release studies. Results: By means of a design 22 a final formulation was obtained that met the requirement of drug released (%) in the sampling times established by the FEUM. The properties of the selected hydrophilic polymer together with the studied variables of polymer proportion (%) and compressive force allowed the release profile to be adapted to the established levels. Conclusions: Hydrophilic matrices were obtained, with a simple and economical formulation that can be used in the treatment with lithium carbonate by prolonged release. [ABSTRACT FROM AUTHOR]

Increasing the lifetime of percutaneous insulin delivery catheters to minimize painful needle sticks increases the risk of infection. To combat surface-adherent bacteria and potential biofilm formation, we developed a method to impregnate levofloxacin antibiotic into the outer polymer of the catheter so that it can leach into the external medium. Complementarily, we developed a method to quantify the concentration of antibiotic to ensure the minimum inhibitory concentration (MIC) is maintained throughout the duration of catheter use. Additionally, we have investigated the extent of antibiotic resistance after a zwitterionic nonfouling coating treatment to ensure suitable release after further surface modification. Levofloxacin was incorporated into the catheter through the swelling of the outer polyurethane of the bilayer catheter and subsequent solvent evaporation. The zone of inhibition was measured over time with S. epidermidis on LB agar plates. The release of levofloxacin was measured using optical absorbance spectroscopy in water and quantified against a linear standard curve at 292 nm. We developed a model using Fick's second law of diffusion to calculate the concentration around the catheter. Visible inhibition of bacterial growth and biofilm formation was shown for up to 38 days. A total of 8–45 µg of antibiotic was released over 26 days and a concentration of 820,000 µg/mL in the 0.17 µL control volume was reached at day 26 for the minimally-loaded samples, an amount many orders of magnitude greater than the MIC. After the nonfouling treatment, the lowest concentration reached was 16 µg/mL after 26 days. In conclusion, we have demonstrated a suitable method to induce antibacterial activity for insulin catheters, maintain the MIC, and sustain antibacterial character following further surface coatings.

This work aimed to formulate xanthan gum microspheres for the encapsulation of metformin hydrochloride, according to the process of ionotropic gelation. The obtained microparticles, based on various fractions of xanthan gum (0.5–1.25), were subjected to different physico-chemical tests and a drug release study. Microspheres with an average size varying between 110.96 μm and 208.27 μm were obtained. Encapsulation efficiency reached 93.11% at a 1.25% biopolymer concentration. The swelling study showed a swelling rate reaching 29.8% in the gastric medium (pH 1.2) and 360% in the intestinal medium (pH 6.8). The drug release studies showed complete metformin hydrochloride release from the beads, especially those prepared from xanthan gum at the concentration of 1.25%, in intestinal medium at 90.00% after 6 h. However, limited and insignificant drug release was observed within the gastric medium (32.50%). The dissolution profiles showed sustained release kinetics. [ABSTRACT FROM AUTHOR]

Background: Alcohol induced dose dumping is a noteworthy question in designing of modified release dosage forms and it led the marketed products withdrawal by regulatory agencies. Diltiazem HCl is a highly watersoluble drug and may undergo faster dissolution in presence of alcohol. The purpose of the present study was to develop extended-release tablets of Diltiazem HCl tablets by direct compression method having robustness in hydro-alcoholic media. Materials and Methods: Using QbD approach, lubricants and polymer as CMAs and drug release as CQAs were identified and further optimization was done by employing 32 factorial design. The extended-release tablets were evaluated for hardness, friability, weight variation and dissolution study was performed in 40% Alcoholic Phosphate buffer pH 5.8. Results: The scientific finding reveals that the concentration of HPMC K-100M DC (12%) and xanthan gums (12%) are capable of providing extended release of drug till the end of 12 hr in pH 5.8 phosphate buffer as well as in 40% Alcoholic Phosphate buffer pH 5.8. Conclusion: These results showed a robust in-vitro drug release profile when exposed to hydro-alcoholic media till 12 hr. Formulation was subjected to accelerated condition for stability testing and was found satisfactory. [ABSTRACT FROM AUTHOR]

This study was aimed formulate of an extended-release tablet of Etodolac for the disease Rheumatoid arthritis were prepared by using different excipient like HPMC, Carbapol, Magnesium Stearate, MCC, at different concentrations. The wavelength of Etodolac 277nm. In precompression Study Powdered drug were evaluated for Angle of repose (36.42°-42.01°), Bulk Density (0.19 - 0.25) g/mL and Tapped density (0.23-0.29) g/mL and compressibility index (13.79-27.58). The results obtained were found to be satisfactory and within the specified limits. After compression parameters like Thickness, Hardness, Weight variation, Friability and In Vitro drug release studies were evaluated. In the present study the effect of types and concentration of polymer were studied on In-Vitro drug release. It shows that increase in concentration of polymer results in the extended drug release for 24 hours. In present studies, formulation containing Carbapol is probably showing release up to 94.55% drug release within 24hrs. [ABSTRACT FROM AUTHOR]

The in vitro release of theophylline from an extended-release dosage form was studied under different hydrodynamic conditions in a United States Pharmacopoeial (USP) dissolution system II and a bespoke in vitro tubular model of the human colon, the Dynamic Colon Model (DCM). Five biorelevant motility patterns extracted from in vivo data were applied to the DCM, mimicking the human proximal colon under baseline conditions and following stimulation using polyethylene glycol or maltose; these represent the lower and upper bounds of motility normally expected in vivo. In the USPII, tablet dissolution was affected by changing hydrodynamic conditions at different agitation speeds of 25, 50 and 100 rpm. Applying different motility patterns in the DCM affected the dissolution profiles produced, with theophylline release at 24 h ranging from 56.74 ± 2.00% (baseline) to 96.74 ± 9.63% (maltose-stimulated). The concentration profiles of theophylline were markedly localized when measured at different segments of the DCM tube, highlighting the importance of a segmented lumen in intestine models and in generating spatial information to support simple temporal dissolution profiles. The results suggested that the shear stresses invoked by the unstimulated, healthy adult human colon may be lower than those in the USPII at 25 rpm and thus insufficient to achieve total release of a therapeutic compound from a hydroxyethyl cellulose matrix. When operated under stimulated conditions, drug release in the DCM was between that achieved at 25 and 50 rpm in the USPII. [ABSTRACT FROM AUTHOR]

Background: Levitiracetam is an antiepileptic medication that falls into the BCS Class I drug classification. It is used to treat specific types of seizures in adults and children with epilepsy because of its high solubility and permeability. Aim: The objective of the present study is to evaluate the extended release tablets of levitiracetam by direct compression using HPMCK100, HPMCK15and Xanthan gum/Ethyl cellulose effect of the dissolution rate by 2 level factorial designs by Design expert software. Materials and Methods: The Design Expert software used to 2 level factorial designs, the three independent components of X1: drug: HPMCK 100, X2: HPMC K15 and X3: Ethyl cellulose/Xanthan gum was used to do analysis of variance (ANOVA), 3D surface plots, counter plots, optimization, and desirability. Fourier-transform infrared spectroscopy was used to investigate drug-excipient compatibility. Results and Conclusion: The drug release from all the tablets was diffusion control as indicated by the linear Higuchi plots. The release data was analyzed Peppas equation the release exponent (n) was found to be in the range 0.76-0.93. Amount all the levetiracetam tablets prepared formulation F2 formulated employing HPMC K100 60 mg, HMPCK15 25 mg, Xanthane gum 25 mg. In the all cases formulations F1, F3, F4, F5,F8 Indicates nonfickain diffusion and F2, F6, F7 Indicates super case II transport as release mechanism. The formulation F2 was released 100% drug release in a 8 hr. It is fulfill specifications for extended release tablets. The results of ANOVA of dependent variables indicated that the individual and combined effect of the 3 factors is significant ( p< 0.05). The design expert software used to find 2 level factorial design, surface, counter plots, optimization and desirability. The optimized formula did better on the desirability level (1.0), indicating that it was a good fit. The FTIR spectra of pure drug and mixture with various excipients, indicates no chemical interaction between drug and excipients. [ABSTRACT FROM AUTHOR]

Aims: Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator that lowers serum triglyceride levels and increases high-density lipoprotein cholesterol levels, is approved for treating dyslipidemia as twice-daily immediate-release (IR) tablets. A once-daily extended-release (XR) tablet has also been developed. We aimed to confirm the non-inferiority of XR (0.2 or 0.4 mg/day; once daily) to IR (0.2 mg/day; twice daily) in lowering triglyceride levels in patients with hypertriglyceridemia., Methods: This phase 3, multicenter, randomized, double-blind study included patients with fasting triglycerides ≥ 200 mg/dL who received IR (0.2 mg/day) or XR (0.2 or 0.4 mg/day). The primary efficacy endpoint was the percentage change in fasting triglyceride levels from baseline to 4, 8, and 12 weeks. Common treatment effects at weeks 4 through 12 were compared between groups using repeated analysis of covariance., Results: In 356 randomized patients, fasting triglyceride levels decreased by 48.0%, 43.8%, and 48.0% with IR 0.2, XR 0.2, and XR 0.4 mg/day, respectively, confirming the non-inferiority of both XR regimens to IR. The proportion of patients who achieved fasting triglycerides ＜150 mg/dL was 45.7%, 37.4%, and 51.7%, while the percentage change of triglycerides in the subgroup with baseline triglycerides ≥ 500 mg/dL was -59.3%, -52.2%, and -66.3% with IR 0.2, XR 0.2, and XR 0.4 mg/day, respectively., Conclusions: XR (0.2 and 0.4 mg/day) was non-inferior to IR (0.2 mg/day). XR 0.4 mg/day demonstrated a more potent triglyceride-lowering effect than XR 0.2 mg/day and should be considered for patients with high triglyceride levels.

Objective: Transdermal route of drug delivery is superior than oral route because it avoids first pass effect, ensures better patient compliance, reduce dosing frequency especially in extended-release formulation and is easy to use. Domperidone HCl is DA2 receptor antagonistic and is used to prevent nausea and vomiting. The objective was to formulate a domperidone HCl extended-release transdermal drug delivery system to treat motion sickness. Methods: Five different formulations were formed using different solvents (methanol and dichloromethane) and polymers (HPMC and Eudragitl-100) by solvent evaporation method. 500mg of domperidone HCl was added in each patch and dibutyl phthalate was added as plasticizer. A 3% w/v PVA layer was used as backing. All these formulations were evaluated for their physicochemical properties (weight variation, thickness, folding endurance and tensile strength), in-vitro drug release, drug contents determination, any incompatibility between drug and excipients by FTIR and DSC and skin irritation. Results: All formulations exhibited good physicochemical properties and percentage drug release during 24 hours was 79.3%, 97.1%, 96.8%, 74.7% and 59.7% respectively. F-YM showed maximum in-vitro drug release. The optimized formulation (F-YM) followed Korsmeyer Peppas release model with n=0.383 showing that the system was following dissolution dependent drug release. No interaction between drug and excipients was detected by DSC and FTIR. No skin irritation was detected. Conclusion: The extended release transdermal patches of domperidone HCl to treat motion sickness were prepared and formulation F-YM showed optimized behavior with maximum in vitro drug release.

This study aimed to produce a gastroretentive floating tablet of Metoprolol succinate and examine the effects of release retardant on in vitro drug release. Metoprolol succinate is a ß1 selective antagonist used as an Anti-hypertensive, Antiarrhythmic, and Anti Angina. Metoprolol succinate has 48% oral bioavailability due to limited absorption from the lower gastrointestinal tract. The Metoprolol succinate floating tablets were designed to increase stomach retention, prolong drug release, and enhance drug bioavailability. To shorten the floating lag time, hydrophilic polymers like Hydroxypropyl methyl cellulose (HPMC K4M, K15M, and K100M), polyethylene oxide (PEO 303), and sodium bicarbonate as a gas-producing agent were incorporated into the formulation of the floating tablets. Different batches of Metoprolol succinate floating tablets were prepared by direct compression. All the formulations were evaluated for various quality control tests, such as weight variation, hardness, friability, swelling index, floating lag time, and total floating time. As a dissolution medium, 0.1 N HCl was used to conduct an in vitro release investigation on the tablets. The present study demonstrates the potential of the sustained-release floating tablets of Metoprolol succinate as an alternative to conventional formulations. [ABSTRACT FROM AUTHOR]

The aim of the present investigation is to develop zaltoprofen-loaded extended-release (ER) pellets formulation by an extrusion-spheronization technique using glyoxalated pre-gelatinized starch (GPS) complex as a novel matrix-forming polymer. The prime objective was to prepare an efficient and robust ER drug delivery system of zaltoprofen. Pellets were characterized by physicochemical, morphological, and solid-state characterization. The formulation was also analyzed for in-vitro drug release and in-vivo pharmacokinetic parameters. The FTIR analysis confirmed the GPS complex formation through the formation of the hemiacetal group while the ketone groups of glyoxal are abolished. Optimized formulation G5 containing 5:8 ratio of GPS complex and MCC showed 99.03 ± 2.12 percent cumulative drug releases in 14 h. The in-vivo study showed decreased Cmax and increased t1/2 compared to bulk zaltoprofen, and hence would be a viable alternative for ER-type formulations. In the author's opinion, the GPS-based ER pellet formulation would be an excellent delivery system for zaltoprofen. [ABSTRACT FROM AUTHOR]

Kuo-Sheng Liu,1 Ching-Wei Kao,2 Yuan-Yun Tseng,3 Shih-Kuang Chen,4 Yu-Ting Lin,4 Chia-Jung Lu,4,5 Shih-Jung Liu4,5 1Department of Thoracic and Cardiovascular Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 2Department of Anesthesiology, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; 3Department of Neurosurgery, New Taipei Municipal Tu-Cheng Hospital (Built and Operated by Chang Gung Medical Foundation), New Taipei City, Taiwan; 4Department of Mechanical Engineering, Chang Gung University, Taoyuan, Taiwan; 5Department of Orthopedic Surgery, Bone and Joint Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, TaiwanCorrespondence: Shih-Jung LiuBiomaterials Lab, Mechanical Engineering, Chang Gung University, 259, Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, TaiwanTel +886-3-2118166Fax +886-3-2118558Email shihjung@mail.cgu.edu.twBackground: Postoperative tissue adhesion is a major concern for most surgeons and is a nearly unpreventable complication after abdominal or pelvic surgeries. This study explored the use of sandwich-structured antimicrobial agents, analgesics, and human epidermal growth factor (hEGF)-incorporated anti-adhesive poly(lactic-co-glycolic acid) nanofibrous membranes for surgical wounds.Materials and Methods: Electrospinning and co-axial electrospinning techniques were utilized in fabricating the membranes. After spinning, the properties of the prepared membranes were assessed. Additionally, high-performance liquid chromatography and enzyme-linked immunosorbent assays were utilized in assessing the in vitro and in vivo liberation profiles of the pharmaceuticals and the hEGF from the membranes.Results: The measured data suggest that the degradable anti-adhesive membranes discharged high levels of vancomycin/ceftazidime, ketorolac, and hEGF in vitro for more than 30, 24, and 27 days, respectively. The in vivo assessment in a rat laparotomy model indicated no adhesion in the peritoneal cavity at 14 days post-operation, demonstrating the anti-adhesive capability of the sandwich-structured nanofibrous membranes. The nanofibers also released effective levels of vancomycin, ceftazidime, and ketorolac for more than 28 days in vivo. Histological examination revealed no adverse effects.Conclusion: The outcomes of this study implied that the anti-adhesive nanofibers with sustained release of antimicrobial agents, analgesics, and growth factors might offer postoperative pain relief and infection control, as well as promote postoperative healing of surgical wounds.Keywords: nanofibrous anti-adhesive membrane, poly(lactic-co-glycolic acid), extended release, vancomycin, ceftazidime, ketorolac, hEGF

The novel food composite hydrogel with delivery function consisting of shrimp powder (SP) and κ-carrageenan (κ-C) was constructed and used for loading apigenin (API). Binary mixtures of liquid SP and κ-C could form gels with solid behavior. Furthermore, the addition of API increased the initial modulus of elasticity of SP/κ-C by approximately 47.3%, as well as a 14.9% reduction in the relaxation time T 23. Moreover, the O-H stretching band and the amide I band of SP/κ-C binary gel loaded with API were blue shifted, and the XRD characteristic peak of API disappeared in SP/κ-C/API. In addition, broken macropores and dispersed patch microstructures were presented in SP and κ-C, whereas the SP/κ-C and SP/κ-C/API hydrogels were homogeneously distributed with dense mesh and solid mesh walls. Hydrophobic interactions were the main forces in the SP/κ-C/API composite hydrogels, which were improved 1.3-fold. Furthermore, SP/κ-C/API was extended and released to more than 55% extent during simulated intestinal colonic digestion. These results suggested that a stable and dense binary gel was formed by SP and κ-C, which could seal and extended release effect of API to the colon. [Display omitted] • Shrimp powder (SP) and κ-carrageenan (κ-C) were prepared into food composite hydrogel. • Liquid SP and κ-C could form gels with solid behavior for protect apigenin (API). • Hydrogen bond and hydrophobic interactions are critical in the SP/κ-C and SP/κ-C/API. • SP/κ-C/API was protected API in gastric and small intestinal simulated digestion. [ABSTRACT FROM AUTHOR]

Long-acting injectable (LAI) opioid formulations mitigate the harm profiles and management challenges associated with providing effective analgesia for animals. A single dose of a long-acting opioid analgesic can provide up to 72 h of clinically relevant pain management. Yet, few of these new drugs have been translated to products for veterinary clinics. Regulatory pathways allow accelerated drug approvals for generic and biosimilar drugs. These pathways depend on rigorous evidence for drug safety and pharmacokinetic evidence demonstrating bioequivalence between the new and the legacy drug. This report reviews the animal PK data associated with lipid and polymer-bound buprenorphine LAI formulations. Buprenorphine is a widely used veterinary opioid analgesic. Because of its safety profile and regulatory status, buprenorphine is more accessible than morphine, methadone, and fentanyl. This review of PK studies coupled with the well-established safety profile of buprenorphine suggests that the accelerated approval pathways may be available for this new family of LAI veterinary pharmaceuticals.

Solid dosage forms based on hypromellose (HPMC) with prolonged/extended drug release are very important from the research and industrial viewpoint. In the present research, the influence of selected excipients on carvedilol release performance from HPMC-based matrix tablets was studied. A comprehensive group of selected excipients was used within the same experimental setup, including different grades of excipients. Compression mixtures were directly compressed using constant compression speed and main compression force. LOESS modelling was used for a detailed comparison of carvedilol release profiles via estimating burst release, lag time, and times at which a certain % of carvedilol was released from the tablets. The overall similarity between obtained carvedilol release profiles was estimated using the bootstrapped similarity factor (f2). In the group of water-soluble carvedilol release modifying excipients, which produced relatively fast carvedilol release profiles, POLYOXᵀᴹ WSR N-80 and Polyglykol® 8000 P demonstrated the best carvedilol release control, and in the group of water-insoluble carvedilol release modifying excipients, which produced relatively slow carvedilol release profiles, AVICEL® PH-102 and AVICEL® PH-200 performed best.

Purpose: A novel once-daily divalproex-extended release (ER) dose formulation has been developed; this formulation prolongs the therapeutic serum levels of the drug, compared with the twice-daily conventional divalproex-delayed release (DR) formulation. This study aimed to systematically examine and compare the efficacy, safety, and retention rates of the ER divalproex (VPA-ER) and conventional DR divalproex (VPA-DR) formulations. Methods: Randomized control trials (RCTs) reporting the efficacy, adverse events (AEs), and medication compliance of ER and DR divalproex were searched in online databases, including PubMed, Embase, and Cochrane Library databases, by searching MeSH words and term words. Observational studies with potential biases were excluded. The metaanalysis was performed using Stata 16.0 software. Findings: Thirteen RCTs, involving 1,028 participants, were included in this meta-analysis. Efficacy, AEs, and drug retention rates were the main study outcomes. According to our study, VPA-ER presented clinically significant benefits compared with the placebo in the population with bipolar disorder (BD) (39.5% versus 27.2%, p < 0.001). A similar efficacy of VPA-ER and VPA-DR in controlling seizures was observed in epilepsy patients (87.4% versus 86.5%, p = 0.769). A significantly lower incidence of AEs was reported in the VPAER group than in the placebo group (26.8% versus 34.8%, p = 0.003). By contrast, there was no evidence of difference in safety between VPA-ER and VPA-DR (29.4% versus 30.5%, p = 0.750). In addition, the drug retention rate was significantly lower in the VPA-ER group than in the placebo group (76.0% versus 82.7%, p = 0.020), especially in migraine patients (p = 0.022) and in patients who were treated for fewer than 4 weeks (p = 0.018). Implications: The efficacy of VPA-ER was significantly superior to that of the placebo treatment, which provided efficacy similar to that of conventional VPA-DR. VPA-ER is well tolerated with a low rate of AEs compared to the placebo. In addition, the acceptable medicine compliance of VPA-ER was conducive to the long-term maintenance treatment of chronic diseases. Although we analyzed open labels and crossover design RCTs, large-scale multicenter studies on the efficacy and medicine compliance of new ER formulations with less AEs are required to validate our conclusion. [ABSTRACT FROM AUTHOR]

Objectives: The objective of the current study was to develop an extended release (XR) tablet formulation for ranolazine using Eudragit L 100-55 and hydroxypropylmethylcellulose (HPMC) K100M in an appropriate composition. Ranolazine, an anti-anginal agent, is mainly used for treating chronic stable angina pectoris. The main advantage of this drug that it exhibits anti-ischemic effect, which was not influenced by either blood pressure or heart rate. Materials and Methods: XR tablets of ranolazine were prepared using variable amounts of Eudragit L 100-55 and HPMC K100M in various proportions as per 32 factorial design by direct compression technique. The amount of polymers with desired sustained drug release was labeled as factors. On other hand, time taken for drug dissolution was labeled as responses (t10%, t50%, t75%, t90%). Results: Nine formulations were obtained as per design, developed, and evaluated for quality control parameters. The obtained results clear that all formulations pass the compendial limits. Data obtained from the dissolution study fitted well to kinetic modeling and kinetic parameters were determined. Polynomial equations were derived for responses and checked for validity. Conclusion: RF5 composed of 31.25 mg of Eudragit L 100-55 and 31.25 mg of HPMC K100M, is the best formulation showing similarity f2: 85.78, f1: 2.32 with the marketed product (RANEXA). Formulation RF5 follows zero order, whereas the release mechanism was found to be non-fickian type (n= 0.65). [ABSTRACT FROM AUTHOR]

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