Drug-excipient Compatibility Research Articles

Formulation, Characterization, and Cytotoxic Effect of Indomethacin-Loaded Nanoparticles.

Indomethacin (IND), classified as class 2 in the Biopharmaceutical Classification System (BCS), has emerged as an anti-inflammatory agent with low solubility and high permeability. Widely used in the treatment of various diseases, such as rheumatoid arthritis and ankylosing spondylitis, this drug is well-known for its adverse effects, particularly in the stomach, and a short biological half-life, which is around 1.5-2 hours. The aim of this study was to overcome the challenges of low solubility, short half-life, and serious side effects occurring with the use of IND-loaded formulations of Solid Lipid Nanoparticles (SLNs) and Polymeric Nanoparticles (PNPs). For PNPs, emulsification/solvent evoporation method was employed, and for SLNs, the hot homogenizaton method was applied. Eudragit® RLPO (RLPO) and Eudragit® RSPO (RSPO) were used as polymers for PNP and Dynasan®116 (DYN) was used as the solid lipid for SLN. Prepared formulations were characterized for Particle Size (PS), Poly-dispersity Index (PDI), Zeta Potential (ZP), Encapsulation Efficiency (%EE), and drug-ex-recipient compatibility using DSC, FT-IR, and 1H NMR; cumulative drug release rates were assessed using HPLC and in vitro cytotoxicities were examined by the MTT assay. Both PNP and SLN formulations' zeta potential, particle size, and PDI results indicated the formulations to have good stability. Encapsulation efficiency values were obtained as desired. Drug-excipient compatibility was proved using DSC, FT-IR, and 1H NMR. In vitro dissolution results have proven both formulations to have longer release than pure indomethacin. In the MTT analysis of indomethacin application for 24 and 48 hours, a linear correlation was observed between drug concentration and cell viability, and it was determined that the PNP formulation exhibited fewer toxic effects among the formulations. This has proven the PNP nanocarrier as safer for normal cells. IND-loaded PNP and SLN formulations have been successfully prepared in this work and they have achieved drug release in the intestine and prolonged the release duration.

Formulation and Evaluation of Mucoadhesive Buccal Tablets of Carvedilol

The aim of the study was to formulate and evaluate the carvedilol buccal tablets using HPMC K4M and xanthan gum as polymer. Buccal tablets of carvedilol were prepared by direct compression technique by using polymer in combination at different concentration. Drug excipient compatibility study indicates that there is no interaction between the excipient and the drug. Total seven batches were prepared and subjected to evaluation parameters. Pre-compression parameters for all batches showed excellent flow propertied of powder bled. Prepared buccal tablets were evaluated for various post compression parameters like hardness, thickness, weight variation, drug content, and friability, % swelling index, muco-adhesive strength and in vitro drug release. The harness of all batches was optimum showed good mechanical strength; thickness of tablets was uniform in all formulations the weight variation test of all the formulation was found to be within the limits of pharmacopoeial standard. % swelling index for all the batch formulation was optimum and seen to increase with increase in polymer concentration. Mucoadhesive strength was also showed acceptable results for all batch formulations which satisfy the need of mucoadhesive tablets. The in vitro dissolution profile of all the formulation showed sustained release of drug, for extended periods of time. The optimized formulation of F4 prepared with was consider as the optimized formulation with respect to drug content, % swelling index, Mucoadhesive strength and in vitro drug release pattern for 8 hrs. Formulation F4 showed highest 98.32±1.55 % drug release at the end of 8 hrs. Optimized formulation F4 was found to be stable during the stability studies for 3 month indicating good stability of the formulation. Keywords: carvedilol, Mucoadhesive strength, Optimized formulation, buccal tablets.

Formulation, Optimization, and Evaluation of Transdermal Patches of Clotrimazole and Betamethasone Dipropionate for Candidiasis

The most effective way to minimize the undesirable side effects of an overdose and to maximize both therapeutic benefits and patient compliance is through TDDS. Due to first-pass metabolism, clotrimazole possesses antifungal action and a half-life of two hours. It has to be dosed frequently. Betamethasone Dipropionate gives anti-inflammatory effect to reduce symptoms of candidiasis. To prolong the release, increase the drug's bioavailability, and increase patient compliance, a transdermal patch containing Clotrimazole and Betamethasone Dipropionate was developed. By adjusting the polymer concentrations through the solvent casting process, various formulations were created. The generated formulations conducted evaluations for several factors, including drug excipient compatibility, drug content, thickness, weight variation, folding durability, moisture uptake, moisture loss, and in vitro drug release. A 32 complete factorial design was used to examine the impact of various polymer concentrations on the reactions of clotrimazole and betamethasone dipropionate, including moisture uptake and percentage of medication released in 12 hours. To determine the kinetics of drug release, in vitro release data were fitted to various models. Batch F5 was considered optimum batch which contained HPMC K4M and Eudragit L-100 in concentrations of 350 and 250 mg respectively. For clotrimazole and betamethasone dipropionate, formulation F5 was shown to have the maximum drug release 75.91% and 67.09%, respectively. The created F5 had the highest drug content, with clotrimazole and betamethasone dipropionate concentrations of 98.78% and 98.82%, respectively.

Preparation and In Vitro Evaluation of Montelukast Sodium-Loaded 3D Printed Orodispersible Films for the Treatment of Asthma.

This research aims to produce orodispersible films (ODFs) and determine their potential use in the oral delivery of montelukast sodium for asthma treatment and allergic rhinitis. ODFs were successfully developed by Three-dimensional (3D) printing using propylene glycol (PG), and hydroxypropyl methylcellulose (HPMC), polyethylene glycol 400 (PEG). Finally, the amount of montelukast sodium in the ODFs was 5% (w/w). Drug-excipients compatibility with Fourier Transformed Infrared (FTIR) spectroscopy, mass uniformity, thickness, disintegration time, folding endurance, moisture absorption, pH, in vitro drug release (dissolution), drug content, moisture loss, moisture content, mechanical properties, and cytotoxicity studies were performed on the prepared films. All formulations disintegrated in approximately 40 s. Over 98% of drug release from all films within 2 min was confirmed. It was reported that Fm1-4 (8% HPMC and 1% PEG) and Fm2-4 (10% HPMC and 3% PEG) are more suitable for drug content, but Fm2-4 may be the ideal formulation considering its durability and transportability properties. Based on the characterization results and in vitro release values, the montelukast sodium ODF can be an option for other dosage forms. It was concluded that the formulations did not show toxic potential by in vitro cytotoxicity study with 3T3 cells. This new formulation can efficiently treat allergic rhinitis and asthma diseases.

Formulation and in-vitro anticancer activity of nilotinib immediate release and ibrutinib sustained release pellets

Background: Blood cancer is a significant contributor to mortality rates worldwide, and its prevalence is projected to rise on a global scale. This trend places considerable strain on healthcare systems and necessitates the expedited development of innovative treatments by pharmaceutical firms to remain competitive. Conventional pellets produce rapid plasma drug levels, but they might cause side effects, decrease effectiveness, and lead to poor therapeutic management. Ibrutinib and Nilotinib are employed to treat leukemia patients. Methodology: The current research aims to formulate, characterize, and anticancer effect of Nilotinib immediate release (NIR) and Ibrutinib sustained release (ISR) seal sugar-coated pellets. Micrometric properties estimated the characterization of the drug pellets, and surface morphology was estimated using scanning electron microscopy. Drug excipient compatibility studies, stability studies, and in-vitro drug release were accessed. Result & Discussion: The results of pellet formulations FNI-1 to FNI-5 showed that FNI-5 formulations showed 100±6.0 µm size and possessed excellent mechanical strength for giving pellets a good self-life; also, due to the higher drug content up to 99%, FNI-5 was the best suited for pellet formulation and because NIR showed 99.18 ± 2.12 drug release at 2h and ISR 99.03±3.74% up to 12h so that anticancer concentration maintained for prolonged period. The standard dose for cytotoxicity against the THP-1 cell line of Nilotinib was found to be 200 mg, and the maintenance oral dose of Ibrutinib was 140mg, with four times the intake of the drug up to 560 mg. In an in vitro study in FNI-5 (final formulation), the dose of Ibrutinib was reduced to 420 mg. Conclusion: A synergistic effect of Ibrutinib and nilotinib drugs was observed in the inhibition of cancer cell growth, with an IC50 value of 4.585 µg/mL

Formulation and evaluation of melatonin as fast dissolving oral strips using combined polymers

Background and objective: Fast-dissolving oral thin film (FDOF) is a novel and most advanced form of solid dosage form that dissolves or disintegrates in 1 minute when put in the mouth without water or chewing. Pre-gastric absorption of FODFs from the mouth, pharynx, and esophagus as saliva flows down into the stomach would improve the therapeutic benefit of the drug as oral films disintegrated in the mouth. The study is designed and purposed to use most water soluble, best type and concentration of polymers to be selected for use in combination to formulate melatonin oral thin films. Different types of synthetic water soluble polymers were utilized the preparation of films (hydroxypropyl methyl cellulose HPMC15M, sodium carboxy methyl cellulose NACMC). Methods: Solvent casting method was performed for preparation of twelve placebo films at the beginning, to obtain and select suitable polymer type and concentration for use in combination to be formulated for drug loading. The films were evaluated for their characteristics like mechanical properties (thickness and folding endurance), surface pH and disintegration time. Percentage of release and assay of melatonin was taken. Comparison studies were performed on melatonin films from this study with melatonin oral disintegrating tablets release profiles. Best batch could be selected. Drug-excipient compatibility carried out as pre formulation study to see whether there is interaction between the drug and excipients used. Results: Results from FT-IR showed no interaction between melatonin and polymers used, the prepared formulations were clear, transparent, non-sticky and easily removed from the plate surface with the thickness ranging from (0.04-0.07) mm depending on the polymer concentration. The times required for the films to disintegrate was ranging from 21-26 seconds, and the majority of melatonin was released within first 2 minutes within the dosage form. Conclusion: Melatonin can be formulated as fast dissolving oral films using combination of water-soluble polymers by solvent casting method to obtain ease of administration without using water during administration, fast onset of action resulted from rapid disintegration.

Formulation and Evaluation of Bilayered Floating Tablets of Aceclofenac

The objective of this study was to create and assess homogeneous bilayered floating tablets of aceclofenac in order to increase the drug's bioavailability and prolong its stomach release. One of the nonsteroidal anti-inflammatory drugs (NSAID) common side effects is poor solubility and minimal stomach retention, which makes it difficult to treat effectively. As matrix-forming polymers, ten formulations (F1–F10) were made with different amounts of HPMC K15 and additional excipients. Physical properties, buoyancy, in vitro drug release, and kinetic modelling were evaluated for each formulation. With a floating lag time of less than one minute and buoyancy maintained for more than 12 hours, Formulation 5 (F5) showed the most promising findings. With 97.01% of aceclofenac released over 12 hours, it showed a regulated drug release pattern that followed the Korsmeyer-Peppas release model well (R2 = 0.9242). Pre-compression and post-compression values for the optimised formulation F5 were adequate, suggesting good flow characteristics and tablet integrity. FTIR spectroscopy was used to verify the drug-excipient compatibility, guaranteeing stability and the lack of interactions. According to these results, aceclofenac's homogenous bilayered floating tablets, specifically formulation F5, may be able to improve gastric retention time and offer a sustained release profile. This could mean that the medication can be used to treat chronic inflammatory conditions more effectively and with better patient compliance. Keywords: gastric retention, bioavailability, drug excipient compatibility.

Assessing the Compatibility of Menatetrenone with Excipients: A Spectroscopic Approach and Implication in Drug Formulation Development.

An experiment was conducted to evaluate the compatibility of menatetrenone with selected pharmaceutical excipients. Fourier Transform Infrared Spectroscopy (FTIR) was used to assess drug-excipient compatibility. The present research systematically investigates the FTIR spectrum of each chemical compound separately and their physical blends, analyzing for possible shifts, alterations or novel peak that may indicate chemical interactions. This study aims to utilize spectral data interpretation to detect potential compatibility problems that may occur while design and production of menatetrenone containing dosage forms ensuring their increased stability and effectiveness. The FTIR results demonstrated that all the pharmaceutical excipients were compatible with menatetrenone. In conclusion, the compatibility of pharmaceutical excipients with menatetrenone was successfully assessed using FTIR that will aid in future design of formulations containing menatetrenone as therapeutic moiety.

Curcumin- β-Cyclodextrin Molecular Inclusion Complex: A Water-Soluble Complex in Fast-dissolving Tablets for the Treatment ofNeurodegenerative Disorders.

Orally disintegrating tablets (ODTs) have become an excellent choice for delivering drugs as their palatability is greatly improved. In this work, β-cyclodextrin has been used to improve the solubility of curcumin by encapsulating it into the hydrophobic cavity for the treatment of neurodegenerative disorders. The current study aimed to present the design, formulation, and optimisation of fastdissolving oral tablets of curcumin- β-cyclodextrin molecular inclusion complex using a 32-factorial design. The drug-excipient compatibility was studied by FTIR spectroscopy. The inclusion complex of curcumin-β-cyclodextrin was prepared using solvent casting and confirmed using XRD studies. Powder blends were evaluated for flow properties. Tablets prepared by direct compression were evaluated for post-compression parameters. Further, the effect of formulation variables, such as sodium starch glycolate (X1) and Neusilin® ULF2 (X2), on various responses, including disintegration time and dissolution at 2 hours, was studied using statistical models. Post-compression parameters, i.e., hardness (4.4-5 kg/cm2), thickness (3.82-3.93 mm), weight variation (±7.5%), friability (< 1%), wetting time (51-85 seconds) and drug content (96.28- 99.32%) were all found to be within the permissible limits and the disintegration time of tablets with super-disintegrants ranged between 45-58 seconds. The in-vitro dissolution profile of tablets showed that higher SSG and Neuslin® ULF2 levels promoted drug release. For statistical analysis, the 2FI model was chosen. Optimised variables for formulation have been determined and validated with the experimental findings based on the significant desirability factor. The current study reveals the validated curcumin-β-cyclodextrin inclusion complex fastdissolving tablets with SSG and Neusilin® ULF2 to be an ideal choice for effectively treating neurodegenerative disorders.

Formulation and Evaluation of Luliconazole nanosponge gel using Experimental design

Different approaches are being in the practice for the topical application of antifungal drugs, although in a few cases, they have been found less efficient because of their poor cutaneous availability and permeability. Luliconazole (LUL) is one of the antifungal medications that is being used for the treatment of various superficial infections. The poor permeability of LUL is regarded to be a factor for its reduced efficacy. Hence, the current study aimed to develop a nanosponge hydrogel that would improve dermal availability and permeability. A set of nanosponge formulations (L1-L18) were designed with the help of central composite design (Design Expert 13, state ease Inc., Minneapolis, MN, USA). L1-L18 was prepared by using the emulsion solvent evaporation technique. The nanosponges were characterized for drug-excipient compatibility (FTIR, P-XRD, and DSC), and particle size, polydispersibility index, zeta potential, entrapment efficiency (EE), and in vitro drug release; further optimized. The optimized nanosponge formulation (L18) was taken to produce six hydrogels (LF1-LF6) of LUL by varied proportions of the gelling agent. In this process, initially, the gel was constituted with Carbopol 934/ sodium CMC/HPMC. Later, attained hydrogel texture was evaluated for its viscosity, swelling, and membrane permeability, followed by in vitro drug release, and antifungal efficacy study. The nanosponge formulations (L1-L17) had an average particle size of 109±0.45 to 386±0.34 nm, entrapment efficiency of 35.45±0.46- 89.65±0.37 % with 84.67±0.54 -99.65±0.48 % of drug release for 8 h. The formulation L18 was predicted with better responses in particle size, EE, and drug release i.e., 378±0.25 nm, 84.65±0.45%, and of 96.18±0.54%, respectively for 8 h. Out of six formulated nanosponge gels (LF1-LF6), LF2 showed an optimal viscosity (25.69 ±0.45 pa.S), pH (6.87±0.56) and % drug release (80.65 ±0.64%) in 8 h. Drug release was governed by non-fickian diffusion mechanisms and zero-order. Developed nanosponge hydrogel was found as stable and had a high rate of permeation with better retention which can be effective enough in topical applications.

Nose to brain delivery of escitalopram-loaded nano-structured lipid carriers thermosensitive gel: Formulation, physiochemical, pharmacokinetic and pharmacodynamics evaluation

The primary focus of the undertaken research was to design and develop poloxamer-based thermosensitive gel system of escitalopram-loaded nano-structured lipid carriers (ESC-NLCs gel) for nose to brain delivery. ESC-NLCs were optimized using Design Expert® (Version 12). The optimized formulation was encompassed in poloxamer-based thermosensitive gel and was characterized accordingly. In vitro release, ex vivo permeation and in vivo brain and plasma pharmacokinetics was investigated. Additionally, behavioral analysis of the lipopolysaccharide (LPS) induced depressed rats was performed followed by immunohistochemistry of the brain hippocampus and cortex regions. Particle size, polydispersity index and zeta potential of the optimized ESC-NLCs were respectively found as 131 nm, 0.278 and −24.9 mV with excellent entrapment efficiency (96 %). The optimized formulation showed suitable morphology, optimum thermal behavior, amorphous nature and drug-excipient compatibility. ESC-NLCs gel displayed sustained in vitro release profile, whereas permeation was enhanced 27-folds. Brain pharmacokinetics of ESC-NLCs explored 9 folds increased drug concentration in brain. Similarly, improved behavioral changes and reduced neuro inflammatory markers (NF-κB and TNF-α) were observed in LPS induced depressed rats after treatment with ESC-NLCs gel. It can be concluded that ESC-NLCs gel has the potential to sustain the drug release, improve the permeation and bioavailability and reduce the depression after nose to brain delivery in animal model.

ZINC PECTINATE-SESBANIA GUM-MEDIATED INTERPENETRATING POLYMER NETWORK-BASED MICROBEADS AS A CANDIDATE FOR FLOATING DRUG DELIVERY OF ESOMEPRAZOLE

This study aimed to develop esomeprazole-loaded zinc-pectinate-Sesbania gum floating microbeads, optionally supplemented with calcium silicate, as a gastro-retentive drug delivery system. The microbeads were produced using the ionic gelation method, with zinc acetate as the crosslinking agent, and were characterized through in vitro studies. The findings revealed that all formulations exhibited high drug encapsulation efficiency and sustained drug release profiles. Polymer ratios, calcium silicate incorporation, and the choice of low-density oils significantly influenced drug encapsulation efficiency and release kinetics. Notably, the B:6 batch, formulated with Sesbania gum and low methoxy pectin, demonstrated outstanding performance, releasing 95.89 ± 1.66% of the drug within 7 h, with a floating lag time of 1.18 ± 0.07 min, indicating promising in vitro gastro-retention capabilities. Analysis of P-XRD, FT-IR, SEM, and DSC data highlighted changes in crystallinity, drug–excipient compatibility, surface morphology, and thermal behavior of esomeprazole and esomeprazole-loaded microbeads. In conclusion, these floating microbeads represent a potential gastro-retentive drug delivery system, offering enhanced buoyancy and prolonged drug release, with potential therapeutic advantages for peptic ulcer management.

DEVELOPMENT, OPTIMIZATION AND IN VITRO CHARACTERIZATION OF HALOPERIDOL NANOCRYSTALS USING 32 FACTORIAL DESIGN

Objective: The main aim of the present study was to improve the dissolution rate of Haloperidol nanocrystals and thereby increase their bioavailability. Haloperidol is a typical antipsychotic drug and it is used to treat schizophrenia as well as acute mania and mixed states associated with bipolar disorder. Haloperidol falls into the Biopharmaceutics Classification System (BCS-II) class of drugs (poorly soluble aqueous and highly permeable) and has poor bioavailability. Methods: The present study involves the preparation and optimization of Haloperidol nanocrystals by the anti-solvent precipitation method using Polaxomer407 and polyvinyl pyrrolidone K30 (PVP K30). The prepared nanocrystals were evaluated for various parameters like particle size, zeta potential, % drug content, % yield, surface morphology, drug-excipient compatibility studies (Fourier-transform infrared spectroscopy (FT-IR) and Differential Scanning Calorimetry (DSC)), and in vitro dissolution studies. Results: Nine preparations were done and the best preparation amongst them was selected for further studies. F7 preparation containingpolaxomer407 and PVP K30 was selected as optimized preparation based on their evaluation parameters. 32 factorial design was used in the preparation. The particle size of the F7 nanocrystals was 300.2±2.7 nm and the zeta potential-36.3±3.2 mV. The % yield was in the range of 63.62±0.3%-98.21±0.8 %. The drug content of various preparations was found to be in the range of 58.46±0.8%-93.54±0.5 %. In vitro dissolution studies showed the highest % drug release for F7(91.54±0.03%) in 10 h. Conclusion: F7 preparation was found to be having acceptable characteristics and thus selected as optimized preparation.

Formulation and In Vitro-Ex vivo Evaluation of Cannabidiol and Cannabidiol-Valine-Hemisuccinate Loaded Lipid-Based Nanoformulations for Ocular Applications

The goal of this investigation is to develop stable ophthalmic nanoformulations containing cannabidiol (CBD) and its analog cannabidiol-valine-hemisuccinate (CBD-VHS) for improved ocular delivery. Two nanoformulations, nanoemulsion (NE) and nanomicelles (NMC), were developed and evaluated for physicochemical characteristics, drug-excipient compatibility, sterilization, thermal analysis, surface morphology, ex-vivo transcorneal permeation, corneal deposition, and stability.The saturation solubility studies revealed that among the surfactants tested, Cremophor EL had the highest solubilizing capacity for CBD (23.3 ± 0.1 mg/mL) and CBD-VHS (11.2 ± 0.2 mg/mL). The globule size for the lead CBD formulations (NE and NMC) ranged between 205 and 270 nm while CBD-VHS-NMC formulation had a particle size of about 78 nm. The sterilized formulations, except for CBD-VHS-NMC at 40 °C, were stable for three months of storage (last time point tested). Release, in terms of CBD, in the in-vitro release/diffusion studies over 18 h, were faster from the CBD-VHS nanomicelles (38 %) compared to that from the CBD nanoemulsion (16 %) and nanomicelles (33 %). Transcorneal permeation studies revealed improvement in CBD permeability and flux with both formulations; however, a greater improvement was observed with the NMC formulation compared to the NE formulation. In conclusion, the nanoformulations prepared could serve as efficient topical ocular drug delivery platforms for CBD and its analog.

Development of Losartan Orally Disintegrating Tablets by Direct Compression: a Cost-Effective Approach to Improve Paediatric Patient's Compliance.

The development of suitable dosage forms is essential for an effective pharmacological treatment in children. Orally disintegrating tablets (ODTs) are attractive dosage forms that avoid swallowing problems, ensure dosage accuracy and are easy to administer as they disintegrate in the oral cavity. This study aimed to develop ODTs containing losartan potassium (LP) for the treatment of arterial hypertension in children. The ODTs, produced by the cost-effective manufacturing process of direct compression, consisted of a mixture of diluent, superdisintegrant, glidant and lubricant. Five superdisintegrants (croscarmellose sodium, two grades of crospovidone, sodium starch glycolate and pregelatinized starch) were tested (at two concentrations), and combined with three diluents (mannitol, lactose and sorbitol). Thus, thirty formulations were evaluated based on disintegration time, hardness and friability. Two formulations, exhibiting the best results concerning disintegration time (< 30s), hardness and friability (≤ 1.0%), were selected as the most promising ones for further evaluation. These ODTs presented favourable drug-excipient compatibility, tabletability and flow properties. The in vitro dissolution studies demonstrated 'very rapid' drug release. Preliminary stability studies highlighted the requirement of a protective packaging. All quality properties retained appropriate results after 12months of storage in airtight containers. In conclusion, the ODTs were successfully developed and characterised, suggesting a potential means to accomplish a final prototype that enables an improvement in childhood arterial hypertension treatment.

Mucoadhesive Buccal Tablet Formulation of Azithromycin dihydrate for treatment of Upper Respiratory Tract Infection

The buccal drug delivery system is a versatile delivery system which can be designed for local or systemic effect. The objective of the study was to developed patient complacent tablet which can give sustain release of antibacterial agent for relief of upper respiratory tract infection. Azithromycin dihydrate is a semi-synthetic macrolide antibiotic widely used to prevent bacterial infections in the upper respiratory tract. The mucoadhesive buccal tablets of azithromycin dihydrate were formulated by varying concentrations of polymers (natural and synthetic), glidant and other excipients. The drug-excipient compatibility studies were carried out through DSC and FTIR studies. The selected excipients were found to be compatible. Further the dry blend of drug-excipients was evaluated for pre-compression properties. The prepared tablets were evaluated as per the general monograph for tablets of IP. The studies were also carried out to evaluate sustained release of the drug and mucoadhesivity of the tablets. A 23 level (2 level and 3 factors) factorial design was navigated to study the effect of natural, synthetic polymers and the glidant on mucoadhesive strength and percentage cumulative drug release at 8 hours. The responsive variables were analysed using ANOVA by Design-Expert version 12.0. It was concluded that these excipients significantly affected the response variables. The optimized tablet formulation was found to have an adequate mucoadhesion and a cumulative percentage release. The final product was performed for accelerated stability studies, optimized formulation was found to be stable at room temperature and accelerated temperature for three months.

Design and Characterization of Hallow Porous Floating Microspheres of Favipiravir

The present investigation deals with the design and characterization of favipiravir floating microspheres for gastro retentive drug delivery system by employing 3² factorial design and also to investigate the main effects of different independent variables on microspheres that float. The emulsion solvent diffusion method was used to manufacture floating microspheres with Eudragit S 100 as the polymer. These microspheres will extend the release of the medicine, reducing the frequency of administration and the harmful effects caused by fluctuations in plasma concentration with conventional dosage forms. The main effect of independent variables like polymer Eudragit S 100 concentrations (50, 100, 150 mg) and stirring time (1, 2 and 3 hours) on the performance of microspheres. Formulated microspheres were characterized for responses including drug release, particle size, and entrapment efficiency and floating time. Based on the results of the responses, the optimized composition was arrived using the response surface method graphical and numerical optimization method using design of experiments (DoE) software. Then, the optimized formulation (OFES) was prepared and evaluated for the four responses compared with predicted values to find the validity of the selected model. The optimized formulation was further analyzed for drug-excipient compatibility by fourier-transform infrared (FTIR), differential scanning calorimetry (DSC), and also analyzed by X-ray diffraction (XRD), scanning electron microscope (SEM) analysis. Further zeta potential and micrometric properties were also observed. The results for the formulation FES 1 to 9 found were, that particles size ranged from 0.192 to 0.277 μm, entrapment efficiency ranged from 68.65 ± 1.9 to 76.25 ± 3.2%, percentage drug release range was from 89.25 ± 0.24 to 93.68 ± 0 .25%, and floating time range was from 12 to 23 hours. As per the design, OFES an optimized formulation fitted with the concentration of Eudragit S 100 of 139.1 mg and stirring time of 1-hour. Regarding the kinetic release, the responses were best fitted with Higuchi model of R² value of 0.9795 with kinetic mechanism of non-fickian diffusion with R² value of 0.9499, indicating good linearity. The combination of different variables and their effects on responses were investigated well using factorial design, and an optimized formulation was developed for favipiravir.

Design, Evaluation and Optimization of Albuterol Sulphate and Theophylline Pulsincap drug delivery system for chronotherapy of Asthma

The aim of the current study was to design and develop and evaluate pulsatile drug delivery system of Albuterol Sulphate and Theophylline for the treatment of Asthma. The capsule body was made water insoluble by cross linked with formaldehyde vaopur. The treatment of Formalin was adopted to modify the gelatin capsule solubility. The formalin residue was carried out by quantitative test. The drug-excipient compatibility is done by FTIR and UV . The pulsincap formulation were prepared by using hydrogel plug of various components. The drug content of the formulation of pulsincap was found to be in the general range. The invitro drug release studies in ph1.2 .6.2 and 7.4 buffern was noticed to be zero percent and capsule was stable for 2 hours drug the studyF5 formulation batch was selected which was best and good formulation and promoted maximum drug release of 96.29% percentage at phosphate buffers when compared with other formulation. Pulsincap formulation can be adopted for optimum delivery of pellets in the treatment as per chronotherapy&#x0D; Keywords: Theophylline, quantitative test, invitro drug release studies, phosphate buffers6.2 and 7.4.

Varenicline and Maltodextrin Combination: A Promising Approach for Reducing Nitrosamine Impurities in Solid Dosage Forms

This research article investigates the use of varenicline and maltodextrin combination to reduce the nitrosamine impurities in varenicline tablets, a medication used to treat nicotine addiction. Nitrosamines are carcinogenic compounds that have been found in varenicline, raising concerns about its safety. Drug excipient compatibility was initially performed with all possible excipients, including maltodextrin, to identify potential approaches for reducing nitrosamine impurities. The results showed that maltodextrin was more effective than other excipients in reducing nitrosamines in the drug product. This finding provided an indication for the use of maltodextrin as a potential solution to the nitrosamine problem in varenicline tablets. The study involved preparing varenicline-maltodextrin formulations and analyzing the formulations for nitrosamine impurities. The finished formulation was prepared by simple mixing of varenicline, maltodextrin, disintegrant, filler, lubricant, and compression using suitable tooling, followed by aqueous film coating. The formulated tablets were tested for assay, content uniformity, dissolution in release media, and multimedia, and the results were found to be satisfactory. The results showed that the varenicline-maltodextrin combination significantly reduced nitrosamine content, and all other parameters were satisfactory. In addition, the nitrosamine impurity levels were significantly reduced to less than 3 ppm after 30 days of storage at 50±2°C/75±5 % RH. Moreover, more than 85% of drug release was observed in all tested release media, meeting the predefined specifications for BCS-based biowaiver. These findings suggest that the use of varenicline and maltodextrin combination is a promising approach to improve the safety of varenicline.

Towards safer and efficient formulations: Machine learning approaches to predict drug-excipient compatibility

Predicting drug-excipient compatibility is a critical aspect of pharmaceutical formulation design. In this study, we introduced an innovative approach that leverages machine learning techniques to improve the accuracy of drug-excipient compatibility predictions. Mol2vec and 2D molecular descriptors combined with the stacking technique were used to improve the performance of the model. This approach achieved a significant advancement in the predictive capacity as demonstrated by the accuracy, precision, recall, AUC, and MCC of 0.98, 0.87, 0.88, 0.93 and 0.86, respectively. Using the DE-INTERACT model as the benchmark, our stacking model could remarkably detect drug-excipient incompatibility in 10/12 tested cases, while DE-INTERACT managed to recognize only 3 out of 12 incompatibility cases in the validation experiments. To ensure user accessibility, the trained model was deployed to a user-friendly web platform (URL: https://decompatibility.streamlit.app/). This interactive interface accommodated inputs through various types, including names, PubChem CID, or SMILES strings. It promptly generated compatibility predictions alongside corresponding probability scores. However, the continual refinement of model performance is crucial before applying this model in practice.