Response Surface Methodology (RSM) approach to formulate and optimize the bilayer combination tablet of Tamsulosin and Finasteride.

An orally administered bilayer tablet with Tamsulosin (TAM) as the sustained release (SR) and Finasteride (FIN) as immediate release (IR) was manufactured. A response surface methodology was employed to formulate bilayer tablets with individual release layers, i.e., sustained and immediate release (SR and IR). Independent variables selected in both cases comprise hydroxypropyl methylcellulose (HPMC) as SR polymer, and avicel PH102 in the inner layer while Triacetin and talc in the outer layer, respectively. Tablets were prepared by direct compression, a total of 11 formulations were prepared for inner layer TAM, and 9 formulations for outer layer FIN were designed; these formulations were evaluated for hardness, friability, thickness, %drug content, and %drug release. A central composite design was employed in response surface methodology to design and optimize the formulation. The percentage of drug released was evaluated by in-vitro USP dissolution method of optimized formulation for 0.5, 2, and 6 hrs, and results were 24.63, 52.96, and 97.68 %, respectively. Drug release data was plotted in various kinetic models using a D.D solver, where drug release was first order that is concentration dependent and was best explained by Korsmeyer-Peppa kinetics, as the highest linearity was observed (R2 = 0.9693). However, a very close relationship was also noted with Higuchi kinetics (R2 = 0.9358). The mechanism of drug release was determined through the Korsmeyer model, and exponent "n" was found to be 0.4, indicative of an anomalous diffusion mechanism or diffusion coupled with erosion.

Comparison of Pakistani CKD-EPI, new Asian-modified CKD-EPI and revised Lund-Malmö study equations in a South Asian CKD population: a study from a Pakistani CKD cohort.

BACKGROUND: Newly proposed estimating glomerular filtration rate equations need to be studied, evaluated and compared for chronic kidney disease staging, diagnosis and medication dosing in South Asians. The objectives of the study were (1) to assess the performance of the CKD-EPIPK, CKD-EPIAsian-Modified, and LMRevised equations in the Pakistani chronic kidney disease population, and (2) to investigate prospective implications on chronic kidney disease classification and end-stage kidney disease prevalence. METHODS: We conducted a cross-sectional analysis on a chronic kidney disease cohort of 385 participants 18 years of age or above. RESULTS: CKD-EPIPK showed the lowest bias (- 1.33 ml/min/1.73 m2), highest precision [IQR, 2.33 (- 2.36, - 0.03)] and enhanced P30 accuracy (89.35%) compared to the CKD-EPIAsian-Modified and LMRevised equations. The mean difference (ml/min/1.73 m2), 95% limit of agreement (ml/min/1.73 m2) of the equations were; CKD-EPIAsian-Modified: - 5.98, - 13.03, LMRevised: - 4.06, - 8.13 and CKD-EPIPK: - 1.18, - 6.14 (P < 0.001). CKD-EPIAsian-Modified and LMRevised showed upward re-classification of the GFR categories compared to the CKD-EPIPK equation except in the G5 category where the highest count (217, 56.36%) was noted for the CKD-EPIPK equation. End-stage kidney disease prevailed in all age groups according to all equations, and the prevalence was high in females in all equations. CONCLUSION: CKD-EPIPK showed the best performance, whereas both CKD-EPIAsian-Modified and LMRevised showed poor performance and did not offer a sufficient advantage in chronic kidney disease classification and end-stage kidney disease prevalence estimation over CKD-EPIPK. Hence, CKD-EPIPK seems ideal for South Asians, thus appropriate measures should be taken for its implementation, at least in Pakistani laboratories.

Solid lipid nanoparticles: a versatile approach for controlled release and targeted drug delivery.

Solid Lipid Nanoparticles (SLN), the first type of lipid-based solid carrier systems in the nanometer range, were introduced as a replacement for liposomes. SLN are aqueous colloidal dispersions with solid biodegradable lipids as their matrix. SLN is produced using processes like solvent diffusion method and high-pressure homogenization, among others. Major benefits include regulated release, increased bioavailability, preservation of peptides and chemically labile compounds like retinol against degradation, cost-effective excipients, better drug integration, and a broad range of applications. Solid lipid nanoparticles can be administered via different routes, such as oral, parenteral, pulmonary, etc. SLN can be prepared by using high shear mixing as well as low shear mixing. The next generation of solid lipids, nanostructured lipid carriers (NLC), can reduce some of the drawbacks of SLN, such as its restricted capacity for drug loading and drug expulsion during storage. NLC are controlled nanostructured lipid particles that enhance drug loading. This review covers a brief introduction of solid lipid nanoparticles, manufacturing techniques, benefits, limitations, and their characterization tests.

Synthesis of Chemically Cross-Linked pH-Sensitive Hydrogels for the Sustained Delivery of Ezetimibe.

In recent years, pH-sensitive hydrogels have been developed for the delivery of therapeutic agents to specific target sites that have a defined pH range. The use of pH-responsive polymers in hydrogels allows drug delivery to the desired pH range of the target organ. The primary aim is to increase the retention time of the drug in the small intestine by utilizing the swelling mechanism of the hydrogel at intestinal pH. In this study, polyethylene glycol (PEG) was used as a polymer to formulate a pH-sensitive hydrogel of Ezetimibe to deliver the drug to the small intestine where it inhibits the absorption of cholesterol. Design Expert software was applied to design and optimize the trial formulations in order to obtain an optimized formulation that has all the desired characteristics of the hydrogels. The PEG/Acrylic Acid hydrogels showed the maximum swelling at pH 6.8, which is consistent with the pH of the small intestine (pH 6-7.4). The maximum entrapment efficiency of the hydrogels was 99%. The hydrogel released 80-90% of the drug within 24 h and followed first-order release kinetics, which showed that the release from the drug was sustained. Hence, the results showed that the choice of a suitable polymer can lead to the development of an efficient drug-loaded hydrogel that can deliver the drug at the specific pH of the target organ.

Synthesis and characterization of self-assembling chitosan-based nanoparticles.

Chitosan (CHT) based biodegradable nanovectors were synthesized and modified with poly ethylene glycol 4000 (PEG-4000). CHT having medium molecular weight with 75% to 85% deacetylation was phthaloylated with phthalic anhydride, followed by PEGylation using PEG-4000. After confirmation of successful PEGylation by fourier transforminfra red spectroscopy (FTIR), the modified polymer was further processed to develop the nanocarrier using ionic gelation method by the addition of sodium tripolyphosphate (NaTPP). The prepared nanocarriers were subjected to physicochemical evaluation. The surface morphology of the particles was observed under scanning electron microscope (SEM), and particle size by dynamic light scattering (DLS) method, which was about 159-170nm in diameter. The zeta potential of the prepared nanovectors was +0.907mV which was due to cationic nature of nanovectors. The cell viability studies were also conducted to find the suitability of the carrier for in-vivo application, using liver cancerous cells (Hep G2). The findings have disclosed the concentration dependent activities of the particles, as viability of the cell was shown to be decreased with the increase in the concentration of the particles. Conclusively, the study was successful in determining the toxicity profile of these nanovectors as these were proved non-toxic at specific concentration.

Hematopoietic effects of Azadirachta indica methanolic extract in cyclophosphamide mediated myelosuppressed albino rat.

Myelosuppression or bone marrow suppression is one of the most common side effects caused by anti-cancer drugs. Certain nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics and viruses like B19 virus can also cause bone marrow suppression resulting in serious consequences like leukopenia, anemia and thrombocytopenia. Currently, it is mainly treated by Filgrastim, use of which is not without side effects. Certain natural drugs can be a safer alternative to treat myelosuppression. Azadirachta indica, commonly known as Neem, is an important medicinal plant of subcontinent. Keeping in view the traditional uses of Neem, present study aims to investigate its potential role in reversing myelosuppression. Albino rats were used to determine hematopoietic activity of Neem leaves after inducing myelosuppression by cyclophosphamide given subcutaneously. Filgrastim was used as reference standard to compare the antimyelosuppressant activity of the drug. The drug was evaluated in three doses i.e. 50mg/kg, 100mg/kg and 200mg/kg body weight, while blood samples were drawn on 0, 1st, 7th, 14th and 21st day. The drug was found to be effective in reversing bone marrow suppression in all three doses based on the hematological parameters (mean WBC, RBC, platelets, Hb, Hct etc.) which improved significantly. The results suggest that the drug can be used as antimyelosuppressant after establishing its safety and identifying its active constituents with their mechanism of action.

Insight on the fractionations and structural characterizations of innovative antidiarrheal compounds screened from leaves of Psidium guajava of local origin in Pakistan.

Numerous ailments have been effectively treated with natural plants for long time all over the world. Plants provided a back bone for the exploration of novel medicinal compounds. Therefore, chief focus of our study was to isolate the biologically active compounds from the plant source and evaluate their antidiarrheal potentials, as diarrhea is still the most dominant disease in developing countries. The isolation and structure elucidation of two new compounds were identified from methanolic and chloroform extracts of Psidium guajava (guava) leaves. Extracts of plants were acquired by successive maceration from dried powder. Castor oil induced diarrheal-model was used to evaluate the antidiarrheal activity and therapeutic response was endorsed to the suppression of normal and wet stools in Spraug Dawley rats. Through the series of fractionations, compound-A was obtained from methanolic extract and named 3-(4-amino 1,3,8-tri-OH 5,6-di-CH3 7-propyl 1,2,3,4,4a,5,8,8a-octahydronaphthalen 2-yl) propanoic3-(4-NH3 7-butyl 1,3,8-tri-OH 5,6-di-CH3 1,2,3,4,4a,5,8,8a-octahydronaphthalen 2-yl)propanoic anhydride. Compound-B was entitled 5-(3-hydroxy-1,4-di-CH3-1,2,3,4,4a,5,8,8a-octahydronaphthalen-2-yl)pent-3-enoic acid was acquired from the chloroform extract. The structure elucidations of both compounds were interpreted through spectroscopic data, including EI-MS, FTIR, 1HNMR and 13C-NMR. The significant antidiarrheal activities were determined with crude extracts and isolated compounds. In inference, present study revealed that substantial antidiarrheal feature of guava is confined to the identified compounds.

Anti myelosuppressant and hematopoietic activities of ethanolic fraction obtained from seeds of Carica papaya L.

Bone marrow suppression is one of the serious consequences of treatment with cytotoxic chemotherapeutic agents such as doxorubicin (DOX). It is very difficult to treat bone marrow suppression caused by anti-cancer drugs. This study was aimed to evaluate hematological effects particularly the antimyelosuppressant effects of ethanolic extract of papaya seeds at 200, 400 and 600 mg/kg daily dose for three weeks in doxorubicin induced hematopoietic suppression in rat model. Hematological parameters were assessed on weekly basis on days 0, 1, 7, 14 and 21. The alcoholic extract was found to cause remission of induced myelosuppression as indicated by a dose dependent increase in WBCs, neutrophils, lymphocytes, platelets, RBCs, Hb, hematocrit & mean corpuscular volume. However, the maximum dose (600mg/kg) of the extract showed maximum activity (p<0.05) in normalizing hematological parameters when compared with group B (induced group) and group A (controlled animals). These effects were compareable with those produced by Filgrastim 5µgm/kg used as standard or reference drug during these experiments. It is concluded from the results that papaya seeds possess myelostimulant activity and can be used to treat myelosuppression caused by chemotherapy. The drug can also be used for curing anemia, thrombocytopenia and immunological disorders characterized by myelosuppression.

Appraisal of organic extracts and isolated compounds of Azadirachta indica for in-vitro antioxidant, acetylcholinesterase and butyrylcholinesterase inhibitory activity.

The current study emphasized on assessment of Antioxidant, Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) inhibitory activity of the crude methanolic and chloroform leaves extracts along with their isolated compounds derived from Azadirachta indica. Phytochemical analysis revealed the manifestation of ancillary metabolites like alkaloid, anthraqinones, catechins, flavonoids, phenolic compounds, saponins, tannins and steroids. Methanolic crude extract of Azadirachta indica leaves revealed comparable antioxidant activity as that of quercetin and propyl gallate. As far as enzyme inhibitory activity was concerned, a significant AChE enzymes inhibition was observed. These findings confirm the traditional use of Azadirachticha indica as medicinal plant in the treatment of mental ailments and anti-inflammatory illnesses. Chloroform crude extract and isolated compounds showed weak antioxidant and enzyme inhibitory activities.

Influence of levodropropizine and hydroxypropyl-ß-cyclodextrin association on the physicochemical characteristics of levodropropizine loaded in hydroxypropyl-ß-cyclodextrin microcontainers: Formulation and in vitro characterization.

BACKGROUND: Poorly water-soluble drugs do not dissolve well in aqueous-based gastrointestinal fluid; therefore, they are not well absorbed. Thus, employing a suitable solubility enhancing technique is necessary for such a drug. Drug/HP­ß­CD complexation is a promising way to improve solubility and dissolution of a poorly water-soluble drug. Levodropropizine was used as a model drug in this study. OBJECTIVES: The purpose of this research was to enhance the aqueous solubility and dissolution rate of levodropropizine by employing the inclusion complexation technique. MATERIAL AND METHODS: A microparticle formulation was prepared from levodropropizine and hydroxypropyl-ß-cyclodextrin (HP­ß­CD) in a 1:1 molar ratio through the spray-drying technique. The host-guest relationship between levodropropizine and HP­ß­CD was also investigated using the molecular docking computational methodology. The aqueous solubility and dissolution rate of levodropropizine in formulations were assessed and compared with those of the drug alone. X-ray diffraction (XRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR) were applied for the solid-state characterization of the prepared samples. RESULTS: According to the research outcomes, the levodropropizine/HP­ß­CD formulation had enhanced the aqueous solubility (351.12 ±13.26 vs 92.76 ±5.00 mg/mL) and dissolution rate (97.83 ±3.36 vs 3.12 ±1.76% in 10 min) of levodropropizine, compared to the plain drug powder. The levodropropizine/ HP­ß­CD formulation had converted the crystalline drug into its amorphous counterpart. Furthermore, no covalent interaction was found to exist between levodropropizine and HP­ß­CD. The spray-dried particles were discrete. Each particle had a shriveled appearance. CONCLUSIONS: The levodropropizine/HP­ß­CD formulation is, therefore, recommended for the more effective administration of levodropropizine through the oral route.