The low water solubility of numerous drug candidates and phytochemicals continues to pose a significant challenge in pharmaceutical development, greatly limiting their bioavailability and therapeutic performance. This review presents a detailed overview of formulation strategies aimed at improving the solubility and dissolution of poorly aqueous-soluble compounds. The biopharmaceutics classification system and the relevance of in vitro-in vivo correlation, as well as key challenges in formulation development, are briefed. Solid-state and particle engineering approaches, including micronization, supercritical fluid technology, electrospinning, and cryogenic techniques, are discussed. Extensive critical examination of amorphous solid dispersions and their preparation methods, as well as crystallization inhibition strategies, is covered. Cocrystallization is highlighted as a promising approach, with emphasis on design principles and preparation methods. Various solubilization techniques, such as pH modification, cosolvency, hydrotropy, micellar solubilization, and cyclodextrin-based complexation, including advanced hybrid systems, are also explored. Emerging solvent platforms, such as deep eutectic systems and lipid-based and nanotechnology-driven approaches, are reviewed for their role in improving solubility and drug delivery. Additionally, enabling technologies such as liquisolid systems and hydrophilic polymers are addressed. Despite notable progress, limitations such as scalability, reproducibility, regulatory constraints, and long-term safety persist. Overall, this review provides integrated insights into formulation design approaches to enhance the solubility and therapeutic efficacy of poorly soluble drugs.

Arthritis is a chronic-inflammatory disorder that impairs joint function and necessitates efficient localised treatment. This research aimed to formulate and optimise leflunomide-loaded nanostructured lipid carriers (NLCs) for topical delivery. Dynasan 114 and corn oil were used as the solid and liquid lipids, respectively, and NLCs were formulated using high-speed homogenisation and probe sonication. Dual experimental design (1) Plackett-Burman for screening, and (2) Box-Behnken for formulation optimisation were employed. The optimised NLCs showed particle size (125.5 nm), PDI (0.188), zeta potential (-15.5 mV), and entrapment efficiency (92.20 ± 1.28%). FT-IR, DSC, P-XRD, and TEM validated the amorphous dispersion of leflunomide within the lipid matrix and the spherical morphology of the NLCs. The optimised NLCs were integrated into a Carbopol 980 NF (0.75%) gel base, demonstrating appropriate rheological properties such as extrudability (176 g), adhesiveness (-112 g), and pH (6.92). The gel formulation demonstrated prolonged drug release (96% over 24 h) and increased ex-vivo permeation with flux of 0.3632 mg/cm2/hour, hence validating enhanced diffusion through the skin barrier. The in-vivo pharmacodynamic study using a carrageenan-induced paw edoema model exhibited an 89.40% reduction in inflammation, exceeding the efficacy of the marketed leflunomide formulation. These findings suggest that the leflunomide-loaded NLC-based gel offers a promising platform for dermal drug distribution and enhanced anti-inflammatory activity.

The low aqueous solubility and permeability of apremilast restricted its clinical efficiency in oral therapy for psoriasis arthritis. This research aimed to develop nanosized lipid carrier with high payload and can provide greater transdermal flux in an attempt to enhance the clinical efficiency of apremilast. Apremilast loaded ethosomes were efficiently formulated by a single-step injection technique. A 3(3) statistical Box-Behnken experimental design was employed to identify the optimum desirability of ethosomes by assessing the effect of three formulation components (soy lecithin, ethanol and apremilast) on responses such as vesicle size, drug entrapment and transdermal flux. The optimized ethosomes were formulated into a gel and evaluated for in vitro and in vivo characteristics including drug release, permeation and pharmacokinetics in rats. The optimization results indicated a significant effect (p < 0.05) of all three formulation variables on the responses evaluated. Optimized ethosomes exhibited spherical shape, nano-size with good payload and greater transdermal flux. The developed ethosomal gel had good physicochemical and rheological properties suitable for topical application and exhibited prolonged drug release by Weibull diffusion. A short lag time and higher transdermal flux (similar to 4 folds higher than control, p < 0.0001) noticed with ethosomes indicates rapid and greater diffusion through the skin barriers. Pharmacokinetic results demonstrated the potential of ethosomes in the transdermal therapy of apremilast as evidenced by the extent of absorption (AUC(0-24), p < 0.0001) when compared with the oral counterpart. In nutshell, the data presented here establish the practical feasibility of ethosomal transdermal delivery and can be an alternative option for oral therapy in treating psoriasis arthritis.

The oral bioavailability of sildenafil citrate is approximately 43

Clinical application of treprostinil in pulmonary arterial hypertension is hampered by adverse effects caused by its high dosing frequency. The objective of this investigation was to Formulate an adhesive-type transdermal patch of treprostinil and evaluate it both in vitro and in vivo. A 32-factorial design was utilized to optimize the selected independent variables (X1: drug amount, X2: enhancer concentration) on the response variables (Y1: drug release, Y2: transdermal flux). The optimized patch was evaluated for various pharmaceutical properties, skin irritation, and pharmacokinetics in rats. Optimization results signify considerable influence (p < 0.0001) of X1 on both Y1 and Y2, as compared to X2. The optimized patch possesses higher drug content (>95%), suitable surface morphology, and an absence of drug crystallization. FTIR analysis revealed compatibility of the drug with excipients, whereas DSC thermograms indicate that the drug exists as amorphous in the patch. The adhesive properties of the prepared patch confirm adequate adhesion and painless removal, while the skin irritation study confirms its safety. A steady drug release via Fickian diffusion and greater transdermal delivery (~23.26 µg/cm2/h) substantiate the potential of the optimized patch. Transdermal therapy resulted in higher treprostinil absorption (p < 0.0001) and relative bioavailability (237%) when compared to oral administration. Overall, the results indicate that the developed drug in the adhesive patch can effectively deliver treprostinil through the skin and could be a promising treatment option for pulmonary arterial hypertension.

The therapeutic effectiveness of paliperidone in the treatment of schizophrenia has been limited by its poor oral bioavailability; hence, an alternative route could be appropriate. This study investigates the feasibility of developing a buccal film impregnated with paliperidone-loaded nanostructured lipid carriers (NLCs) and assesses the potential to enhance its bioavailability. Box–Behnken-based design optimization of NLCs was performed by examining the particles’ physical characteristics. The polymeric film was used to load optimized NLCs, which were then assessed for their pharmaceutical properties, permeability, and pharmacokinetics. The optimization outcomes indicated that selected formulation variables had a considerable (p < 0.05) impact on responses such as particle size, entrapment efficiency, and % drug release. Desired characteristics such as a negative charge, higher entrapment efficiency, and nanoparticles with ideal size distribution were shown by optimized NLC dispersions. The developed film demonstrated excellent physico-mechanical properties, appropriate texture, good drug excipient compatibility (chemically stable formulation), and amorphous drug nature. A sustained Weibull model drug release (p < 0.0005) and superior flux (~5-fold higher, p < 0.005) were seen in NLC-loaded film compared to plain-drug-loaded film. The pharmacokinetics profile in rabbits supports the goal of buccal therapy as evidenced by significantly higher AUC0–12 (p < 0.0001) and greater relative bioavailability (236%) than the control. These results support the conclusion that paliperidone-loaded NLC buccal film has the potential to be an alternate therapy for its effective administration in the treatment of schizophrenia.

Dolutegravir’s therapeutic effectiveness in the management of neuroAIDS is mainly limited by its failure to cross the blood–brain barrier. However, lipid-based nanovesicles such as nanoemulsions have demonstrated their potential for the brain targeting of various drugs by intranasal delivery. Thus, the purpose of this study was to develop a Dolutegravir-loaded nanoemulsion-based in situ gel and evaluate its prospective for brain targeting by intranasal delivery. Dolutegravir-loaded nanoemulsions were prepared using dill oil, Tween® 80, and Transcutol® P. Optimization of the nanoemulsion particle size and drug release was carried out using a simplex lattice design. Formulations (F1–F7 and B1–B6) were assessed for various pharmaceutical characteristics. Ex vivo permeation and ciliotoxicity studies of selected in situ gels (B1) were conducted using sheep nasal mucosa. Drug targeting to the brain was assessed in vivo in rats following the nasal delivery of B1. The composition of oil, surfactant, and cosurfactant significantly (p < 0.05) influenced the dependent variables (particle size and % of drug release in 8 h). Formulation B1 exhibits pharmaceutical characteristics that are ideal for intranasal delivery. The mucosal steady-state flux noticed with BI was significantly greater (p < 0.005) than for the control gel. A histopathology of nasal mucosa treated with BI showed no signs of toxicity or cellular damage. Intranasal administration of B1 resulted in greater Cmax (~six-fold, p < 0.0001) and AUC0−α (~five-fold, p < 0.0001), and decreased Tmax (1 h) values in the brain, compared to intravenous administration. Meantime, the drug level in the plasma was relatively low, suggesting less systemic exposure to Dolutegravir through intranasal delivery. In summary, the promising data observed here signifies the prospective of B1 to enhance the brain targeting of Dolutegravir by intranasal delivery and it could be used as a feasible and practicable strategy for the management of neuroAIDS.

Poor aqueous solubility besides extensive hepatic first effect significantly decreases the oral absorption of levosulpiride, which in turn minimizes its therapeutic effectiveness. Niosomes have been extensively investigated as a transdermal vesicular nanocarrier to increase the delivery of low permeable compounds into and across the skin. This research work was to design, develop and optimize levosulpiride-loaded niosomal gel and to evaluate its prospects for transdermal delivery. The Box-Behnken design was used to optimize niosomes by analyzing the impact of three factors (cholesterol; X1, Span 40; X2, and sonication time; X3) on the responses (particle size, Y1, and entrapment efficiency, Y2). Optimized formulation (NC) was incorporated into gel and evaluated for pharmaceutical properties, drug release study, ex vivo permeation, and in vivo absorption. The design experiment data suggest that all three independent variables influence both response variables significantly (p < 0.01). Pharmaceutical characteristics of NC vesicles showed the absence of drug excipient interaction, nanosize (~102.2 nm), narrow distribution (~0.218), adequate zeta potential (−49.9 mV), and spherical shape, which are suitable for transdermal therapy. The levosulpiride release rates varied significantly (p < 0.01) between niosomal gel formulation and control. Greater flux (p < 0.01) was observed with levosulpiride-loaded niosomal gel than with control gel formulation. Indeed, the drug plasma profile of niosomal gel was significantly higher (p < 0.005), with ~3 folds higher Cmax and greater bioavailability (~500% higher; p < 0.0001) than its counterpart. Overall, these findings imply that the use of an optimized niosomal gel formulation can increase the therapeutic efficacy of levosulpiride and may represent a promising alternative to conventional therapy.

Bacterial pectinase enzyme is very much important at industrial level for different processes This present study focus on bacterial pectinase. Pectinase producing bacterial spp.is screen out from soil. About seven cultures of bacterial spp. were isolated from farmland soil sample using pectin agar plates. The selected isolates showed the zone of hydrolysis to confirmed the production of pectinase from the isolates. Among them the culture S4 showed prominent zone of hydrolysis surrounding the colony. Pectinase activity of each isolate were checked at an interval of 24 hrsusing DNSA method to access the enzyme efficiency produced by respective isolates. Keeping the ideal growth conditions the highest pectinase activity obtained among isolates was 11.43 U/ ml, by culture S4.Optimum condition for pectinase production was found at 72hrs. incubation period, 37˚C temperature and alkaline pH of 10 could be the optimum cultural conditions for bacterial strain S4. Bacterial strain S4 gave 40.85 U/ml partially purified enzyme.

Introduction: Philadelphia chromosome is well-known chromosomal abnormality in Chronic Myeloid Leukaemia (CML). However, B-acute lymphoblastic leukemia (B-ALL) with Philadelphia-positive (Ph′+) is a neoplasm of lymphoblast committed to the B-cell lineage, occurs in about 20 % to 30 % of all cases in adults. The incidence increases with age, up to 50 % of ALL diagnosed in individual’s ≥50 years old. The clinical presentation of B-ALL Ph′+ is similar to B-ALL but is more common in adults than in children. Case Report: A 64 year-old female patient presented to Medicine OPD with complaints of fever, weakness and uneasiness, along with old history of endometrial carcinoma. She was further investigated and diagnosed as De-novo case of B-precursor ALL with positive BCR-ABL fusion gene as no chemotherapy was given for previously reported malignancy. Conclusion: Here, we like to emphasize that overlapping symptoms may lead to delay in diagnosis. Hence, clinician should always investigate the patient thoroughly, in order to diagnose the patient on time. So that, treatment can be started as early as possible to avoid fatal outcomes in Ph′ Chromosome positive B cell ALL, as it has worst prognosis.

Agriculture need novel technology as well as sustainability for high crop yield with good nutritional values. Microbes play an essential role in maintaining soil fertility. Specially Rhizobia contribute in supplying nitrogen source in soil as well as to plant roots. Rhizospheric microbes have major role in balancing nutrients. Present study represents primary understanding of different rhizobia species from different leguminous plant

Introduction: A unique white cell abnormality called transient abnormal myelopoiesis [TAM] is found in approximately 10% of neonates with Down’s syndrome. Material & method: Medical record of a case of confirmed TAM in Down’s syndrome was reviewed in retrospect at Desai Metropolis laboratory. The co-relation of prenatal ultrasonographic findings, maternal screen results, fetal blood analysis, flow cytometry, karyotyping and the postnatal clinical course were done. Result: A case of TAM associated with Down’s syndrome was confirmed in November 2021. A complete blood count done on 2nd day of life showed abnormal leukocytosis with blast cells. TAM spontaneously resolved after 15 days of birth. Conclusion: Fetal TAM is a self-limiting condition which requires supportive care. In the neonatal period, most cases of TAM have a favorable outcome from this preleukemic condition, but some progress to leukemia. Investigation of TAM will continue to strongly influence basic and clinical research into development of hematological malignancies.

The clinical efficacy of antiretroviral therapy in NeuroAIDS is primarily limited by the low perfusion of the drug to the brain. The objective of the current investigation was to design and develop an in situ mucoadhesive gel loaded with darunavir to assess the feasibility of brain targeting through the intranasal route. Preliminary batches (F1–F9) were prepared and evaluated for various pharmaceutical characteristics. A full factorial design of the experiment was applied to optimize and assess the effect of two influencing variables (Carbopol 934P (X1) and Poloxamer 407 (X2)) on the response effects (gelation temperature (Y1) and % drug release (Y2) at 8 h). The data demonstrate that both influencing variables affect the response variables significantly (p < 0.05). The optimized formulation (F7) exhibited favorable rheological properties, adequate mucoadhesion, sustained drug release, and greater permeation across the nasal mucosa. An in vitro ciliotoxicity study confirms the nontoxicity of the optimized in situ gel (D7) on the nasal mucosa. An in vivo pharmacokinetic study in rats was performed to assess drug targeting to the brain following the nasal application of the selected in situ gel (D7). Significantly higher (p < 0.0001) Cmax (~4-fold) and AUC0-α (~3.5-fold) values were noticed in the brain after nasal application, as compared to the intravenous route. However, less systemic exposure to darunavir was noticed with nasal therapy, which confirms the low absorption of the drug into the central compartment. Overall, the data here demonstrate that the optimized in situ mucoadhesive nasal gel is effective in targeting darunavir to the brain by the nasal route and could be a viable option for the treatment of NeuroAIDS.

The oral administration of naproxen, a non-steroidal analgesic, antipyretic, anti-inflammatory drug, is associated with various gastrointestinal side effects including peptic ulcer and gastritis. The objective of the present research was to evaluate the prospective of transdermal delivery of naproxen using proniosomes as a vesicular carrier and its comparison with oral therapy. Drug loaded proniosomes were prepared by coacervation phase separation, which comprising of spans/tweens, lecithin, and cholesterol. The influence of formulation components was evaluated to assess their impact on the entrapment efficiency, vesicle size, zeta potential, in vitro release and ex vivo permeation. The results signify that the type of surfactant influenced the entrapment efficiency, vesicle size and zeta potential values of prepared proniosomes. All formulations displayed nano-sized vesicles with small polydispersity index value showing narrow particle size distribution. Hydrophilic tweens produced larger vesicles and exhibited greater drug release than their hydrophobic spans counterparts. Prepared proniosomes exhibited distinct drug release profile (p < 0.05) as compared to control HPMC hydrogel. The proniosomal formulation (F3) containing span 60 showed superior transdermal flux (1.10 +/- 0.24 mu g cm-2 h-1) when compared to other non-ionic surfactants tested. In vivo data demonstrated both anti-inflammatory and antinociceptive efficiency of transdermal naproxen proniosome formulation (F3) was equivalent to the oral marketed naproxen tablets at same dose. Overall the results of present investigation suggest that proniosomes can be considered as a practicable and feasible alternative for oral naproxen delivery.

Plastic materials have been used in various ways such as packaging material, glass wares, certain parts of instruments of various grades, many more. As plastic products are not easily decomposed and accumulate in environment. This has created an adverse effect on our ecosystem. Bioplastics are best alternative to overcome these issues and reduce damages in ecosystem. Bioplastics are easily and speedily degrade under natural environmental conditions. Polyhydroxybutyrate or PHB is a bioplastic, one of the best natural polymer and alternative of synthetic plastic material. Bioplastic are comparative more flexible to convert into various forms also. Normally, it is a lipid reserve material produce in adverse or under stress conditions and stored within the cell wall of micro-organisms. Poly-3-hydroxybutyrate (PHB) is a natural biopolymer produce by wide range of microbes which is a storage granule used by microbes as an energy as well as carbon source.this microbes includes from extremophiles to mesophiles. The objective of our work was to isolate potential PHB producing bacteria using agro-residues as carbon sources within natural environment conditions. This work describes the understanding of microbes that are involved in the degradation of both natural and synthetic polymers.Also to contribute in green environment by providing eco- friendly product.

Asenapine, an atypical antipsychotic agent, has been approved for the acute and maintenance treatment of schizophrenia and manic episodes of bipolar disorder. However, the extensive hepatic metabolism limits its oral bioavailability. Therefore, the objective of the current investigation was to develop sublingual film containing asenapine to enhance the therapeutic efficacy. Sublingual films containing asenapine were fabricated using polyethylene oxide and hydroxypropyl methylcellulose by solvent casting method. Design of experiment was used as a statistical tool to optimize the proportion of the film-forming polymers in order to establish the critical quality attributes of the drug formulation. The process was studied in detail by assessing risk of each step as well as parameters and material attributes to reduce the risk to a minimum. A control strategy was defined to ensure manufacture of films according to the target product profile by evaluation of intermediate quality attributes at the end of each process step. Results of optimized formulations showed rapid disintegration, adequate folding endurance, good percentage elongation, tensile strength, and viscosity. Besides, the results from the in vitro dissolution/ex vivo permeation studies showed rapid dissolution (100% in 6 min) and higher asenapine permeation (~ 80% in 90 min) through the sublingual epithelium. In vivo study indicates greater asenapine absorption (31.18 ± 5.01% of administered dose) within 5 min and was comparable with marketed formulation. In summary, the designing plan to develop asenapine formulation was successfully achieved with desired characteristics of the delivery tool for sublingual administration.

Being a candidate of BCS class II, dolutegravir (DTG), a recently approved antiretroviral drug, possesses solubility issues. The current research was aimed to improve the solubility of the DTG and thereby enhance its efficacy using the solid dispersion technique. In due course, the miscibility study of the drug was performed with different polymers, where Poloxamer 407 (P407) was found suitable to move forward. The solid dispersion of DTG and P407 was formulated using solvent evaporation technique with a 1:1 proportion of drug and polymer, where the solid-state characterization was performed using differential scanning calorimetry, Fourier transform infrared spectroscopy and X-ray diffraction. No physicochemical interaction was found between the DTG and P407 in the fabricated solid dispersion; however, crystalline state of the drug was changed to amorphous as evident from the X-ray diffractogram. A rapid release of DTG was observed from the solid dispersion (>95%), which is highly significant (p<0.05) as compared to pure drug (11.40%), physical mixture (20.07%) and marketed preparation of DTG (35.30%). The drug release from the formulated solid dispersion followed Weibull model kinetics. Finally, the rapid drug release from the solid dispersion formulation revealed increased Cmax (14.56 μg/mL) when compared to the physical mixture (4.12 μg/mL) and pure drug (3.45 μg/mL). This was further reflected by improved bioavailability of DTG (AUC: 105.99±10.07 μg/h/mL) in the experimental Wistar rats when compared to the AUC of animals administered with physical mixture (54.45±6.58 μg/h/mL) and pure drug (49.27±6.16 μg/h/mL). Therefore, it could be concluded that the dissolution profile and simultaneously the bioavailability of DTG could be enhanced by means of the solid dispersion platform using the hydrophilic polymer, P407, which could be projected towards improved efficacy of the drug in HIV/AIDS.

Cellulolytic waste is superfluous in lithosphere and its conversion is one of the basic necessities.In current research, we have screen out potential bacterial isolates that were found capable fordegradation of cellulose material. They can easily convert it into simple usable form of sugar. Allisolates were capable to use cellulose in natural environmental condition such as pH, humidityand moderate temperature range. Isolation was done using to carboxymethycellulose agarmedium. While, the isolates were cultivated by submerged fermentation method (Smf). Amongall isolates Bacullis pumilus was found most potent strain for cellulose degradation and forproduction of cellulase at large scale