Advanced Targeted Drug Delivery of Bioactive Nanomaterials in the Management of Cancer.

Cancer is defined as the unchecked expansion of aberrant cells. Radiation, chemotherapy, and surgery are currently used in combination to treat cancer. Traditional drug delivery techniques kill healthy proliferating cells when used over prolonged periods of time in cancer chemotherapy. Due to the fact that the majority of tumor cells do not infiltrate right away, this is particularly true when treating solid tumors. A targeted drug delivery system (TDDS) is a tool that distributes medication to a selected bioactive location in a controlled manner. Nanotechnology-based delivery techniques are having a substantial impact on cancer treatment, and polymers are essential for making nanoparticulate carriers for cancer therapy. The advantages of nanotherapeutic drug delivery systems (NDDS) in terms of technology include longer half-life, improved biodistribution, longer drug circulation time, regulated and sustained drug release, flexibility in drug administration method, higher drug intercellular concentration, and others. The benefits and drawbacks of cancer nanomedicines, such as polymer-drug conjugates, micelles, dendrimers, immunoconjugates, liposomes, and nanoparticles, are discussed in this work, along with the most recent findings on polymer-based anticancer drugs.

Quality by design approach for oral bioavailability enhancement of irbesartan by self-nanoemulsifying tablets.

The present investigation was aimed to develop self-nanoemulsifying tablets (SNETs) as novel nanosized solid oral dosage forms for Irbesartan (IRB). In the first part of the investigation, IRB-loaded self-nanoemulsifying drug delivery systems (SNEDDS) were developed using Capryol 90 - Cremophor RH40 - Transcutol P as three component (oil - surfactant - cosurfactant) SNEDDS system. On the basis of ternary phase diagram IRB-loaded SNEDDS were optimized by using Design of Experiments (DoE) and Principal component analysis (PCA) with amount of oil and surfactant: cosurfactant ratio (Km) as factors. The optimized batch of IRB-loaded SNEDDS comprised of 31.62% w/w of Capryol 90 as oil phase, 49.90% w/w Cremophor RH40 as surfactant and 18.48% w/w of Transcutol P as cosurfactant exemplified a mean globule size as 23.94 nm. Further, with an aim to provide enhanced patient compliance the optimized batch of liquid SNEDDS was transformed into SNETs by liquisolid compaction technique. Solid state characterization of IRB-loaded liquisolid mixtures revealed a decrease in the magnitude of crystallinity of IRB. The results of in vitro drug release study of optimized batch of IRB-loaded SNET illustrated a remarkable improvement in the dissolution rate as compared to marketed tablets (Avapro® 75). The results of in vivo pharmacokinetic study on Wister rats revealed 1.78-fold enhancement in oral bioavailability for IRB-loaded SNETs against marketed tablets. The present study proposed SNEDDS as one of the suitable approach for developing nanosized solid oral dosage forms of poorly water soluble drugs like Irbesartan.

Formulation and evaluation of periodontal in situ gel.

BACKGROUND: The present study was aimed to develop and optimize in situ gel for the treatment of periodontal disease. MATERIALS AND METHODS: Temperature-sensitive in situ gel containing 0.1% w/v Chlorhexidine hydrochloride was formulated by cold method using different polymers. Preliminary study was carried out to optimize different types and concentration of polymers such as Poloxamer 188, Poloxamer 407, Gellan gum, and Carbopol 934P. Central composite design was employed for optimization of the effect of independent variables such as Poloxamer 407 and Carbopol 934P on responses such as gelation temperature, spreadability, cumulative percentage release at 2 h, and time for 50% drug release (t50 %). Each formulations were evaluated for clarity, pH, gelation temperature, spreadability, drug content, in vitro drug release, t50 %, and cumulative percentage drug release at 2 h. RESULTS: Results of evaluation parameters revealed that the drug release, gelation temperature was considerably decreased with increasing t50 % as the concentration of each polymer was increased. The desirability function was utilized to find out optimized formulation of the factorial design. Formulation F6 showed the highest overall desirability of 0.6283 and, therefore, this formulation was considered to be the optimized formulation. The % relative error was calculated, which showed that observed responses were in close agreement with the predicted values calculated from the generated regression equations. CONCLUSION: The clarity, pH, drug content of all formulations was found to be satisfactory. Further, all the formulations showed sustained drug release for a period of 6 h, which satisfied to treat periodontal disease.

Preparation and evaluation of agglomerated crystals by crystallo-co-agglomeration: an integrated approach of principal component analysis and Box-Behnken experimental design.

Poor mechanical properties of crystalline drug particles require wet granulation technique for tablet production which is uneconomical, laborious, and tedious. The present investigation was aimed to improve flow and mechanical properties of racecadotril (RCD), a poorly water soluble antidiarrheal agent, by a crystallo-co-agglomeration (CCA) technique. The influence of various excipients and processing conditions on formation of directly compressible agglomerates of RCD was evaluated. Principal component analysis and Box-Behnken experimental design was implemented to optimize the agglomerates with good micromeritics and mechanical properties. The overall yield of the process was 88-98% with size of agglomerates between 351 and 1214 µm. Further, higher rotational speed reduced the size of agglomerates and disturbed sphericity. The optimized batch of agglomerates exhibited excellent flowability and crushing strength. The optimized batch of RCD agglomerates was characterized by fourier transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffractometry and gas chromatography which illustrated absence of drug-excipient interaction with minimal entrapment of residual solvent. Hence, it may be concluded that both excipients and processing conditions played a vital role to prepare spherical crystal agglomerates of RCD by CCA and it can be adopted as an excellent alternative to wet granulation.

Development and Evaluation of Carbon Nanotubes Doped Sustained Release Microspheres of Metoprolol Tartrate.

A highly water soluble antihypertensive drug, metoprolol tartrate (MT) was selected as a model drug for preparation ofmulti-walled carbon nanotubes (MWCNTs) impregnated ethyl cellulose (EC) microspheres with aim to increase encapsulation efficiency and sustained release rate. Carbon nanotubesdrug adsorbate (MWCNTs:MT) loaded EC microspheres were optimized by Central Composite Design of experiment. The effects of independent variables (MWCNTs:MT and EC:adsorbate) were evaluated on responses like entrapment efficiency (EE) and time required for 50% drug release (t50). Furthermore, desirability approach was adopted to select best batch. The results revealed improvement in encapsulation efficiency for MWCNTs:MTloaded EC microspheres. In vitro drug release study exhibited complete release form drug alone microspheres within 14 h while MWCNTs impregnated EC microspheres exhibited only 50-60 % drug release in 14 h.The optimized batch was further characterized by various instrumental analysis which endorse encapsulation of MWCNTs:MT adsorbate inside the matrix of EC microspheres which resulted in enhanced encapsulation and sustained effect of MT.

Influence of excipients and processing conditions on the development of agglomerates of racecadotril by crystallo-co-agglomeration.

PURPOSE: The purpose of the present investigation was to improve the flow and mechanical properties of racecadotril by a crystallo-co-agglomeration (CCA) technique. Direct tableting is a requirement of pharmaceutical industries. Poor mechanical properties of crystalline drug particles require wet granulation which is uneconomical, laborious, and tedious. MATERIALS AND METHODS: The objective of this work was to study the influence of various polymers/excipients and processing conditions on the formation of directly compressible agglomerates of the water-insoluble drug, racecadotril, an antidiarrheal agent. The agglomerates of racecadotril were prepared using dichloromethane (DCM)-water as the crystallization system. DCM acted as a good solvent for racecadotril as well as a bridging liquid for the agglomeration of the crystallized drug and water as the nonsolvent. The prepared agglomerates were tested for micromeritic and mechanical properties. RESULTS: The process yielded ~90 to 96% wt/ wt spherical agglomerates containing racecadotril with the diameter between 299 and 521 µ. A higher rotational speed of crystallization system reduces the size of the agglomerates and disturbs the sphericity. Spherical agglomerates were generated with a uniform dispersion of the crystallized drug. CCA showed excellent flowability and crushing strength. CONCLUSION: Excipients and processing conditions can play a key role in preparing spherical agglomerates of racecadotril by CCA, an excellent alternative to the wet granulation process to prepare intermediates for direct compression.

Solubility of aceclofenac in polyamidoamine dendrimer solutions.

In the present study we investigated the effect of polyamidoamine (PAMAM) dendrimers on the aqueous solubility of aceclofenac. The aqueous solubility of aceclofenac was measured in the presence of dendrimers in distilled water. The effect of variables, such as pH condition, concentration, temperature and generation (molecule size) of dendrimer, has been investigated. Results showed that the solubility of aceclofenac in the dendrimer solutions was proportional to dendrimer concentration. The order in which the dendrimers increased the solubility at a constant pH condition was G3 > G0. The influence of dendrimer solution pH on the solubility enhancement of aceclofenac suggests that it involves an electrostatic interaction between the carboxyl group of the aceclofenac molecule and the amine groups of the dendrimer molecule. The solubility of aceclofenac was inversely proportional to the temperature of dendrimer solution.Different generation (G0 and G3) PAMAM dendrimers have the potential to significantly enhance the solubility of poor water-soluble drugs.