Combined treatment of prednisone and hydroxychloroquine may improve outcomes of frozen embryo transfer in antinuclear antibody-positive patients undergoing IVF/ICSI treatment.

BACKGROUND: The influence of anti-nuclear antibody (ANA) on induced ovulation was controversial, and the effect of prednisone plus hydroxychloroquine (HCQ) treatment on frozen embryo transfer outcomes of in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) for ANA-positive women was unclear. METHODS: Fifty ANA-positive women and one-hundred ANA-negative women matched for age and anti-Mullerian hormone (AMH) were included from a Reproductive Medical Central of a University Hospital. Sixty-one oocytes pick-up (OPU) cycles in ANA+ group and one-hundred OPU cycles in ANA- group were compared; 30 frozen embryo transfer cycles without treatment and 66 with prednisone plus HCQ treatment among ANA-positive women were compared. RESULTS: There was no statistical difference in number of retrieved oocytes (13.66 ± 7.71 vs 13.72 ± 7.23, p = .445), available embryos (5.23 ± 3.37 vs 5.47 ± 3.26, p = .347), high-quality embryos (3.64 ± 3.25 vs 3.70 ± 3.52, p = .832), and proportion of high-quality embryos (26.5% vs. 26.7%, p = .940). Biochemical pregnancy rate (33.3% vs. 68.2%, p < .05), clinical pregnancy rate (20.0% vs. 50.1%, p < .05), and implantation rate (5.6% vs. 31.8%, p < .05) were lower, and pregnancy loss rate (83.3% vs. 23.1%, p < .05) was higher in patients with treatment than no treatment. CONCLUSION: The influence of ANA on number of retrieved oocytes, available embryos, high-quality embryos, and proration of high-quality embryos was not found. The treatment of prednisone plus HCQ may improve implantation rate, biochemical pregnancy rate, and clinical pregnancy rate, and reduce pregnancy loss rate in frozen embryo transfer outcomes for ANA-positive women.

The role of human C5a as a non-genomic target in corticosteroid therapy for management of severe COVID19.

Complement system plays a dual role; physiological as well as pathophysiological. While physiological role protects the host, pathophysiological role can substantially harm the host, by triggering several hyper-inflammatory pathways, referred as "hypercytokinaemia". Emerging clinical evidence suggests that exposure to severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), tricks the complement to aberrantly activate the "hypercytokinaemia" loop, which significantly contributes to the severity of the COVID19. The pathophysiological response of the complement is usually amplified by the over production of potent chemoattractants and inflammatory modulators, like C3a and C5a. Therefore, it is logical that neutralizing the harmful effects of the inflammatory modulators of the complement system can be beneficial for the management of COVID19. While the hunt for safe and efficacious vaccines were underway, polypharmacology based combination therapies were fairly successful in reducing both the morbidity and mortality of COVID19 across the globe. Repurposing of small molecule drugs as "neutraligands" of C5a appears to be an alternative for modulating the hyper-inflammatory signals, triggered by the C5a-C5aR signaling axes. Thus, in the current study, few specific and non-specific immunomodulators (azithromycin, colchicine, famotidine, fluvoxamine, dexamethasone and prednisone) generally prescribed for prophylactic usage for management of COVID19 were subjected to computational and biophysical studies to probe whether any of the above drugs can act as "neutraligands", by selectively binding to C5a over C3a. The data presented in this study indicates that corticosteroids, like prednisone can have potentially better selectively (Kd ∼ 0.38 µM) toward C5a than C3a, suggesting the positive modulatory role of C5a in the general success of the corticosteroid therapy in moderate to severe COVID19.

On-Demand Reversible UV-Triggered Interpenetrating Polymer Network-Based Drug Delivery System Using the Spiropyran-Merocyanine Hydrophobicity Switch.

A reversible switchable on-demand UV-triggered drug delivery system (DDS) based on interpenetrating polymer networks (IPNs) with silicone as the host polymer and spiropyran (SP)-functionalized guest polymer is designed and demonstrated. The photo-responsive IPNs provide a new triggered drug delivery concept as they exploit the change in intermolecular interactions (work of adhesion) among the drug, matrix, and solvent when the incorporated hydrophobic SP moieties transform into the hydrophilic merocyanine form upon light irradiation without degradation and disruption of the DDS. The change in how the copolymer composition (hydrophilicity and content) and the lipophilicity of the drug (log P) affect the release profile was investigated. A thermodynamic model, based on Hansen solubility parameters, was developed to design and optimize the polymer composition of the IPNs to obtain the most efficient light-triggered drug release and suppression of the premature release. The developed IPNs showed excellent result for dopamine, l-dopa, and prednisone with around 90-95% light-triggered release. The model was applied to study the release behavior of drugs with different log P and to estimate if the light-induced hydrophobic-to-hydrophilic switch can overcome the work of adhesion between polymers and drugs and hence the desorption and release of the drugs. To the best of our knowledge, this is the first time that work of adhesion is used for this aim. Comparing the result obtained from the model and experiment shows that the model is useful for evaluating and estimating the release behavior of specific drugs merocyanine, IPN, DDS, and spiropyran.

Carbon isotopic characterization of prednisolone and prednisone pharmaceutical formulations: Implications in antidoping analysis.

Twenty-two pharmaceutical formulations containing prednisolone or prednisone commercially available in Italy, Belgium, Spain, Brazil, and India were analyzed through a specific gas chromatography combustion isotope ratio mass spectrometry (GC-C-IRMS) method. All of them showed typical non-endogenous δ13 C values, except for the Belgian nasal spray, Sofrasolone®, with a less depleted 13 C content (-17.84 ± 0.18‰). Observational studies were performed on two volunteers in therapy with Sofrasolone® to confirm the applicability of the method and to suggest adequate interpretation criteria also in the case of drugs with less negative δ13 C values. Urine samples were collected before, during, and within the 36 hours after the administration of the spray. Both δ13 C values and urinary concentrations of prednisolone and prednisone were evaluated. All samples were subjected to an adequate pre-treatment (enzymatic hydrolysis, liquid/liquid extraction, and two sequential HPLC steps) before injection to the GC-C-IRMS instrument, according to the method recently developed and validated in our laboratory. Pregnanediol (PD), tetrahydro-11-deoxycortisol (THS), and pregnanetriol (PT) were selected as endogenous reference compounds (ERC). The excretion profile was estimated through liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) method used routinely for the quali-quantitative detection of glucocorticoids. δ13 C values and urinary levels of prednisolone and prednisone were also determined after the intake of one single vial of Sintredius®, a prednisolone oral formulation with a conventional more negative δ13 C value (-29.28 ± 0.25‰). Finally, the potential masking effect that combined therapy with Sofrasolone® and Sintredius® could induce on the IRMS findings was investigated.

Synthesis of some steroidal mitocans of nanomolar cytotoxicity acting by apoptosis.

Several steroids (abiraterone, prednisone, testosterone, cholesterol) and the BCL-2 inhibitor bexarotene were used as starting materials to synthesize iperazinyl-spacered rhodamine B conjugates. The conjugates were screened for their cytotoxicity in SRB assays against several human tumor cell lines and found to be active in a low µM to nM range. The conjugate derived from testosterone held an EC50 = 59 nM against MCF-7 tumor cells and acted mainly by necrosis. The prednisone conjugate, however, was less cytotoxic but acted mainly by apoptosis and held a moderate selectivity against MCF-7 tumor cells.

Δ1-Dehydrogenation and C20 Reduction of Cortisone and Hydrocortisone Catalyzed by Rhodococcus Strains.

Prednisone and prednisolone are steroids widely used as anti-inflammatory drugs. Development of the pharmaceutical industry is currently aimed at introducing biotechnological processes and replacing multiple-stage chemical syntheses. In this work we evaluated the ability of bacteria belonging to the Rhodococcus genus to biotransform substrates, such as cortisone and hydrocortisone, to obtain prednisone and prednisolone, respectively. These products are of great interest from a pharmaceutical point of view as they have higher anti-inflammatory activity than the starting substrates. After an initial lab-scale screening of 13 Rhodococcus strains, to select the highest producers of prednisone and prednisolone, we reported the 200 ml-batch scale-up to test the process efficiency and productivity of the most promising Rhodococcus strains. R. ruber, R. globerulus and R. coprophilus gave the Δ1-dehydrogenation products of cortisone and hydrocortisone (prednisone and prednisolone) in variable amounts. In these biotransformations, the formation of products with the reduced carbonyl group in position C20 of the lateral chain of the steroid nucleus was also observed (i.e., 20ß-hydroxy-prednisone and 20ß-hydroxy-prednisolone). The yields, the absence of collateral products, and in some cases the absence of starting products allow us to say that cortisone and hydrocortisone are partly degraded.

Performance of Nb/BDD material for the electrochemical advanced oxidation of prednisone in different water matrix.

Glucocorticoids are widely used to treat a variety of diseases. Consequently, these compounds have been found in water and wastewater matrix. Despite studies have proven its toxicity, just a few works investigate techniques to degrade and mineralize them. To solve this issue, this work presents the degradation and mineralization of prednisone (PRED) by electrochemical advanced oxidation (EAO) using a boron-doped diamond supported on niobium (Nb/BDD) anode in synthetic and real wastewater. Cyclic voltammetry (CV) was performed to investigate the PRED oxidation mechanisms. CV suggest that PRED will be oxidized via HO• and other oxidants generated from the ions present in the liquid matrix (S2O82-, SO4•-, HClO, ClO- etc.). Different EAO conditions as initial pH (3, 7 and 11) and applied current densities (5, 10 and 20 mA cm-2) were evaluated. The best result was obtained at alkaline pH (11) and a current density of 20 mA cm-2, achieving 78% of degradation and 42% of mineralization. Using the best conditions, the EAO was applied as a polishing treatment stage to remove PRED from a biological pre-treated municipal wastewater spiked with PRED. The results indicate that EAO applied in the real matrix provides better results than the synthetic solution, probably associated with the presence of ions that can be electrochemically converted into oxidant species, resulting in higher kinetic constant, mineralization current efficiency and lower energetic consumption. Therefore, the EAO process without the addition of chemicals has proven to be an effective alternative as a tertiary treatment of municipal wastewater contaminated with PRED.

Kinetics and mechanistic study on degradation of prednisone acetate by ozone.

Prednisone acetate (PNSA) is one of the regular glucocorticoid medicines that have been detected in surface water. In this work, the removal of PNSA by ozone was systematically studied under various conditions, and degradation intermediates and reaction pathways were proposed. The results showed that aqueous ozonation was able to remove PNSA effectively, and low pH favored this reaction. The addition of tertiary butanol did not inhibit the oxidation of PNSA by ozone, suggesting that the degradation was caused mainly by the direct oxidation effect of ozone molecules. Moreover, the presence of carboxylated or hydroxylated multiwalled carbon nanotubes can enhance the removal efficiency of PNSA by ozone. Under neutral and acidic conditions, the degradation of PNSA followed pseudo-first-order reaction. Seven intermediates were detected via liquid chromatography-mass spectrometry, and the degradation pathways were then proposed by considering the relative charge density of the frontier orbitals calculated with the Gaussian program. The electrophilic reaction and the Criegee mechanism were the primary reaction mechanisms in the degradation of PNSA by ozone. Formic acid, acetic acid, and oxalic acid were detected as the final reaction products via ion chromatography. Additionally, the aquatic toxicity of the ozonation products was predicted using ECOSAR method. The biodegradation potentials of the pollutant and the ozonation products were estimated using BIOWINTM, suggesting that O3 treatment could significantly enhance the biodegradable potentials of PNSA and its transformation intermediates in the biological post-treatment process. This work can provide useful information for the treatment of PNSA-containing wastewaters.

Blend of cellulose ester and enteric polymers for delayed and enteric coating of core tablets of hydrophilic and hydrophobic drugs.

The focus of this work was to explore feasibility of using blends of cellulose esters (CA 320S, CA 3980-10 or CAB 171-15) and enteric polymers (C-A-P, Eudragit® L100 or HPMCP HP-55) for delayed and enteric coating of tablets containing either diclofenac sodium (DFS, high dose) or prednisone (PDS, low dose) drug. The core tablets of DFS or PDS were coated with polymer blends to achieve approximate weight gain of 5% and 10%. The coated tablets were characterized for dissolution (0.1 N HCl and phosphate buffer pH 6.8) and surface morphology. The surface morphology of CA 398-10 or CAB 171-15 based polymer blends was rough and fibrous. Less than 0.5% drug was dissolved in 120 min from 5% w/w coated tablets in acid-phase dissolution testing. The dissolution in phosphate buffer pH 6.8 medium varied from 16.2 ±â€¯0.2 to 98 ±â€¯2.1%, and 30.1 ±â€¯0.5% to 101.7 ±â€¯3.4% in 120 min from DFS and PDS coated tablets, respectively. Dissolution was less in CA 320S based blends compared to CA 398-10 or CAB 171-15 blends in phosphate buffer medium. Furthermore, there were no significant differences observed in dissolution profiles of coated tablets of DFS or PDS. This can be explained by dose of the drugs. Additionally, dissolution was higher in tablets coated with enteric polymer alone compared with the blends. In conclusion, core tablets can be coated with cellulose ester and enteric polymers blend to impart both delayed and enteric release feature to the tablets containing hydrophilic or hydrophobic drug.

Two-component cross-linkable gels for fabrication of solid oral dosage forms.

Current three-dimensional (3D) printing techniques involve the solidification of the injected materials by means of UV irradiation, evaporation of organic solvents, or harsh heating and cooling processes. These methods limit the printing of many sensitive bio-active molecules such as proteins. We describe a novel 3D printing technique based on two complementary liquid copolymers, PEG4-PCL-SC and PEG4-PCL-NH2, that are injected in a coordinated fashion and react with each other to form a pre-designed 3D pill. Printed pills swelled about 400% over 3 h, followed by moderate disintegration. Both prednisone and bovine serum albumin were incorporated into the printed pill, but while most of the prednisone was released depending on the ratio between the two complementary pre-polymers, only 40% of the bovine serum albumin was released from the pill. This unique 3D printing apparatus can be used to produce pills at home when the required medication does not handle current production techniques well and may have other possible biomedical applications. However, before this system can be considered for pharmaceutical applications, the low printing resolution, attributable to the slow gelation kinetics and the viscosity of the pre-polymers, should be addressed.

LC-MS/MS assay for the quantification of testosterone, dihydrotestosterone, androstenedione, cortisol and prednisone in plasma from castrated prostate cancer patients treated with abiraterone acetate or enzalutamide.

Prostate cancer is the most common malignancy among men in the Western world. Treatment of this patient population, e.g. by (chemical) castration, is primarily focused on depletion of tumor-stimulating androgens, with testosterone being the major androgenic hormone. After initial therapy, prostate cancer may progress to metastatic castration-resistant prostate cancer. Anti-hormonal drugs abiraterone acetate and enzalutamide are commonly used to treat patients with this disease as both drugs reduce tumor growth and increase time to tumor progression. To evaluate the pharmacodynamic effects of anti-hormonal drugs in this patient population, we developed an LC-MS/MS method for the quantification of testosterone, dihydrotestosterone, androstenedione, cortisol and prednisone in human plasma. The validated assay ranges from 10-10,000 pg/mL for testosterone and androstenedione, 100-10,000 pg/mL for dihydrotestosterone, 50-5000 pg/mL for cortisol and 500-50,000 pg/mL for prednisone. Intra-assay and inter-assay variabilities were within ±15% of the nominal concentrations for quality control (QC) samples at low, medium and high concentrations and within ±20% at the lower limit of quantification (LLOQ), respectively. The applicability of the method was demonstrated in plasma from patients with metastatic castrated-resistant prostate cancer using either abiraterone acetate or enzalutamide.

Bacterial CYP154C8 catalyzes carbon-carbon bond cleavage in steroids.

Here, we report the first bacterial cytochrome P450, CYP154C8, that catalyzes the C-C bond cleavage reaction of steroids. A major change in product distribution is observed with CYP154C8, when the reactions are supported by NADPH and spinach redox partners ferredoxin and ferredoxin reductase, compared with previously reported reactions supported by NADH and redox partners containing putidaredoxin and putidaredoxin reductase. The NMR-based structural elucidation of reaction products reveals 21-hydroxyprednisone as the major product for prednisone, while the other product is identified as 1-dehydroadrenosterone obtained due to C-C bond cleavage. A similar pattern of product formation is observed with cortisone, hydrocortisone, and prednisone. The reaction catalyzed by CYP154C8 in the presence of oxygen surrogates also prominently shows the formation of C-C bond cleavage products.

Small volume method for drug release screening using ultrasonic agitation.

Drug release testing plays a major role along all parts of the dosage form development and manufacturing process. However, official methods to perform this type of testing are often resource intensive and require highly specialized facilities. Affordable and accessible methods for studying drug release behavior are currently lacking. This work presents a small volume approach to solid dissolution and drug release testing of solid dosage forms using ultrasonic agitation. Cavitation and acoustic streaming were generated by a microprobe horn delivering a 40 kHz acoustic signal into a 50 mL test vessel. These two phenomena resulted in breakdown of and release of drug from tablet samples. Prednisone Performance Verification Tablets were used as model tablets to study the effect of system parameters on the drug release process. The effects of these parameters on the acousto-hydrodynamic environment were studied using streak photography and hydrophone measurements. Drug release behavior showed a slow/fast threshold transition separated by a highly variable regime as a function of the system parameters. Observations from drug release experiments and results from acoust-hydrodynamic characterization experiments suggested that this transition is dominated by acoustic streaming. This method represents a screening method to probe relative differences in dosage form composition and acts as a complimentary approach to official testing methods. The small volume format of this test has potential applications in the study of drug release properties from low-dose and novel solid dosage forms as well as reduced cost and increased accessibility of release testing for post-manufacturing tablet quality screening, a current need in low- and middle-income countries.

Preparation and application of a molecular capture for safety detection of cosmetics based on surface imprinting and multi-walled carbon nanotubes.

A novel composite material for prednisone molecular capture (PS-MC) was prepared by surface imprinting technique in combination with a polyethylene filter plate coated with multi-walled carbon nanotubes for the first time. PS-MC was achieved by using prednisone as the template molecule, 3-aminopropyltriethoxysilane as the monomer, and tetraethoxysilane as the cross-linker. The structure, morphology, and thermal stability of the prepared PS-MC were studied by fourier-transform infrared spectrometry, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, and thermogravimetric analysis. PS-MC was assessed by re-binding experiments such as adsorption kinetics, adsorption isotherms, molecular identification, and applied to the separation and enrichment of prednisone in cosmetics. The results indicated that PS-MC has rapid binding kinetic, high adsorption capacity, and favorable reusability. The imprinted materials were coupled with HPLC to selectively separation, purification, and detection of prednisone from spiked cosmetic samples. The recoveries of spiked cosmetic samples were in the range of 83.0-106.0%, with relative standard deviations of less than 2.10%, and the limit of detection of 5 ng/mL (S/N = 3).

A study on the removal of prednisone from aqueous solutions by adsorption onto a vegetal activated carbon.

This study evaluated the prednisone removal from aqueous solutions using adsorption by an activated carbon of vegetal origin (VAC). A central composite rotatable design (CCRD) and the response surface methodology (RSM) were used to verify the influence of the parameters: pH, adsorbent dose and prednisone concentration in a batch adsorption process. Among the analyzed parameters, only the adsorbent dose and the prednisone concentration were statistically significant (α = 0.05) and the critical values obtained were adsorbent dose: 1.87 g/L, pH 7.56 and prednisone concentration: 3.66 mg/L with 77.51% of prednisone removal by VAC. The kinetic study of the adsorption of prednisone reached the equilibrium in 4 h. The pseudo-first-order model described adequately the kinetics data behavior. The equilibrium experimental data obtained at different temperatures showed that the VAC has a maximum adsorption capacity of 18.04 mg/g at a temperature of 30 °C. The prednisone removal decreased by the increasing temperature and the Langmuir isotherm well described the experimental data (R² > 0.98). Thermodynamic results shown that the prednisone removal of aqueous solutions by VAC is spontaneous and favorable process.

A 26-week feasibility study comparing the efficacy and safety of modified-release prednisone with immediate-release prednisolone in newly diagnosed cases of giant cell arteritis.

OBJECTIVE: A feasibility study to assess efficacy and safety of modified release (MR) prednisone (Lodotra™) compared to immediate release (IR) prednisolone in patients with newly diagnosed giant cell arteritis (GCA). METHODS: Twelve patients with new diagnosis of GCA were initially treated with high-dose prednisolone (40-60 mg) daily for 4 weeks and then randomized to two open arms to continue tapering steroid treatment with either standard IR prednisolone or MR prednisone. Patients were reviewed every 2 weeks either face to face or by telephone, for a total of 26 weeks. Disease activity, steroid-related side effects, sleep disturbance, fatigue scores and blood tests were systematically monitored. The primary endpoint (efficacy) was defined as the proportion of patients achieving persistent clinical disease control (without features of active disease and remaining flare free at 26 weeks) in each arm. RESULTS: At 26 weeks, 6/7 patients taking MR prednisone were in persistent control, compared with 4/5 receiving IR prednisone. One patient in each group suffered a disease flare necessitating an increased steroid dose. There were no statistically significant differences between the groups in terms of reduction in inflammatory markers, Health Assessment Questionnaire, visual analogue scale, fatigue and improvement in EuroQol 5D scores. CONCLUSION: This trial shows that MR prednisone appears to be a safe and effective treatment for GCA with a similar outcome profile to standard IR prednisolone.

Chemical Pathways of Corticosteroids, Industrial Synthesis from Sapogenins.

Corticosteroids are products of high industrial and commercial importance. There are dozens of different synthesis published for all of them. Some are coming from academia and some from industry. Here, industrial processes for the synthesis of prednisone, prednisolone, hydrocortisone, dexamethasone, betamethasone, and methylprednisolone are described. The starting material is diosgenin and the desired molecules are reached due to a good combination of chemistry and biotechnology that was developed along the second part of the twentieth century.

Silica-based systems for oral delivery of drugs, macromolecules and cells.

According to the US Food and Drug Administration and the European Food Safety Authority, amorphous forms of silica and silicates are generally recognized to be safe as oral delivery ingredients in amounts up to 1500mg per day. Silica is used in the formulation of solid dosage forms, e.g. tablets, as glidant or lubricant. The synthesis of silica-based materials depends on the payload nature, drug, macromolecule or cell, and on the target release (active or passive). In the literature, most of the examples deal with the encapsulation of drugs in mesoporous silica nanoparticles. Still to date limited reports concerning the delivery of encapsulated macromolecules and cells have been reported in the field of oral delivery, despite the multiple promising examples demonstrating the compatibility of the sol-gel route with biological entities, likewise the interest of silica as an oral carrier. Silica diatoms appear as an elegant, cost-effective and promising alternative to synthetic sol-gel-based materials. This review reports the latest advances silica-based systems and discusses the potential benefits and drawbacks of using silica for oral delivery of drugs, macromolecules or cells.

Palatability of a novel oral formulation of prednisone in healthy young adults.

OBJECTIVES: Prednisone is a widely used anti-inflammatory for a variety of conditions. While oral liquid formulations of prednisone enable weight-based dosing, children frequently find them to be objectionable due to bitter taste. This limitation of prednisone can adversely impact patient acceptance and may result in non-compliance. Efforts to mask flavours often result in poorly controlled, heterogeneous particle distributions and can provide ineffective taste masking. The present work utilized a novel drug delivery technology developed by Orbis Biosciences, Inc., to create an oral taste-masked formulation of prednisone. METHODS: The study examined the palatability of Orbis' microsphere prednisone formulation in healthy young adults (n = 24). Four test articles were used in the study including a reference formulation (Roxanne Laboratories), a control and the test formulation (Orbis) prepared in two different ways. Study participants were randomized in a crossover design. KEY FINDINGS: Results indicated that the test prednisone formulation was indistinguishable from the control, and both were preferable to the reference formulation in every category of palatability assessed using a validated 9-point Hedonic Scale. The data also suggested that preparing the microsphere suspension immediately before administration results in the most ideal palatability properties. CONCLUSIONS: In conclusion, the novel microsphere formulation technology was effective in taste-masking prednisone.

Quality by Design Empowered Development and Optimisation of Time-Controlled Pulsatile Release Platform Formulation Employing Compression Coating Technology.

The research was envisaged for development of time-controlled pulsatile release (PR) platform formulation to facilitate management of early morning chronological attacks. The development was started using prednisone as a model drug wherein core tablets were prepared using direct compression method and subsequently compression-coated with ethylcellulose (EC)-hydroxypropyl methylcellulose (HPMC) excipient blend. Initially, quality target product profile was established and risk assessment was performed using failure mode and effect analysis. In an endeavour to accomplish the objective, central composite design was employed as a design of experiment (DoE) tool. Optimised compression-coated tablet (CCT) exhibited 4-6 h lag time followed by burst release profile under variegated dissolution conditions viz. multi-media, change in apparatus/agitation and biorelevant media. Afterwards, five different drugs, i.e. methylprednisolone, diclofenac sodium, diltiazem hydrochloride, nifedipine and lornoxicam, were one-by-one incorporated into the optimised prednisone formula with replacement of former drug. Change in drug precipitated the issues like poor solubility and flow property which were respectively resolved through formulation of solid dispersion and preparation of active pharmaceutical ingredient (API) granules. Albeit, all drug CCTs exhibited desired release profile similar to prednisone CCTs. In nutshell, tour de force of research epitomised the objective of incorporating diverse drug molecules and penultimately obtaining robust release profile at varying dissolution conditions.