Anita Lalwani

Modulation of Drug Release Rate of Diltiazem-HCl from Hydrogel Matrices of Succinic Acid-Treated Ispaghula Husk

The feasibility of using succinic acid-treated ispaghula husk in matrix-based tablets of diltiazem–HCl was investigated. The sample prepared using 4:1 weight ratio of ispaghula husk to succinic acid showed improved swelling and gelling. A 32 factorial design was employed to investigate the effect of amount of succinic acid-treated ispaghula husk and dicalcium phosphate (DCP) on the percentage of the drug dissolved in 60, 300, and 480 min from the compressed tablets. The results of multiple linear regression analysis revealed that the significance of the amount of succinic acid-treated ispaghula husk was greater in magnitude than that of the amount of DCP in controlling the drug release. Acceptable batches were identified from a contour plot with constraints on the percentage drug released at the three sampling times. A mathematical model was also evolved to describe the entire dissolution profile. The results of F-test revealed that the Higuchi model fits well to the in vitro dissolution data. The tablets showed considerable radial and axial swelling in distilled water. Succinic acid-treated ispaghula husk can be used as an economical hydrophilic matrixing agent.

Preparation and evaluation of an ispaghula based directly compressible matrixing agent for controlled release

Preparation and evaluation of an ispaghula based directly compressible matrixing agent for controlled release The objective of the present investigation was to prepare and evaluate an ispaghula husk based directly compressible (DC) adjuvant that can be used as matrixing agent using an agglomeration technique. Addition of hydroxypropyl methylcellulose was found necessary to improve cohesion. Lactose (X1), calcium hydrogen phosphate dihydrate (X2) and Avicel PH101 (X3), used along with ispaghula in preparation of agglomerates, were selected as three independent variables in a simplex lattice design affecting compressional and dissolution characteristics of the drug from the DC adjuvant. The agglomerates were evaluated for their flow properties. Tablets were prepared using 70% agglomerates and 30% acetaminophen, a poorly compressible drug, and were subjected to in vitro drug release study. Amounts of the drug released at the end of 60 min (Y60), 300 min (Y300) and 480 min (Y480) were selected as dependent variables in a simplex lattice design. Batch IH05 that contained lactose and calcium hydrogen phosphate dihydrate in a 1:2 ratio could control the release for 12 hours and thus form the basis for twice a-day-dosing. Priprava i vrednovanje matriksnog agensa na bazi ispagule za kontrolirano oslobađanje Cilj rada bila je priprava i vrednovanje pomoćne tvari za izravnu kompresiju dobivene iz ljuski ispagule, primjenjive u izradi pripravaka metodom aglomeracije. Dodatak hidroksipropil metilceluloze bio je neophodan za povećanje kohezije. U pripravi aglomerata s ispagulom upotrebljeni su laktoza (X1), kalcijev hidrogenfosfat dihidrat (X2) i Avicel PH101 (X3). U eksperimentalnom dizajnu (simplex lattice design) te tri tvari izabrane su kao nezavisne varijable. Proučavan je njihov utjecaj na kompresibilnost i oslobađanje ljekovite tvari iz pripravka dobivenih izravnom kompresijom te svojstva tečnosti aglomerata. Tako dobiveni aglomerati upotrebljeni su za pripravu tableta teško kompresibilne tvari acetaminofena (omjer aglomerata i ljekovite tvari 7:3). Količine oslobođene tvari in vitro pri kraju 60 min (Y60), 300 min (Y300) i 480 min (Y480) bile su zavisne varijable. Iz pripravka IH05 koji sadrži laktozu i kalcijev hidrogenfosfat dihidrat u omjeru 1:2 kontrolirano se oslobađa ljekovita tvar tijekom 12 sati, što je dobar temelj za doziranje dva puta dnevno.

QbD based development of proliposome of lopinavir for improved oral bioavailability

&NA; Aim of present work was to apply quality by design (QbD) principles for the development of proliposome of poorly soluble lopinavir (LPV). The patient‐centric quality target product profile (QTPP) was defined and critical quality attributes (CQAs) earmarked. Risk assessment studies were carried out to identify the probable risks affecting the CQAs of the product. On the basis of preliminary study, lipid:drug ratio and amount of carrier were selected as critical material attributes (CMAs) and were optimized by face centered central composite design. Liposome vesicle size, drug entrapment efficiency and % drug release after 60 min were selected as CQAs and mathematical relationship between CQAs and CMAs was derived using multiple linear regression analysis. Optimum composition of CMAs, identified using numerical optimization and desirability function, demonstrated excellent entrapment efficiency (> 90%), drug release characteristics (> 95% in 60 min) and had vesicle size of 659.7 ± 23.1 nm. Solid state characterization studies (Differential Scanning Calorimetry, scanning electron microscopy and X‐ray diffraction) were performed for optimized proliposome, suggested transformation of crystalline to amorphous form. Oral bioavailability study in Wistar rats revealed that LPV proliposome exhibited 2.24 and 1.16 fold higher bioavailability than pure LPV and available commercial formulation of LPV/RTV (lopinavir + ritonavir), respectively. Stability study of the optimized LPV loaded proliposome was performed as per ICH guideline and was found to be stable for period of 6 months. Overall results of the study indicate that the proliposome offers advantages of enhanced oral bioavailability for poorly soluble LPV. Graphical abstract Figure. No caption available.

Statistical modeling, optimization and characterization of solid self-nanoemulsifying drug delivery system of lopinavir using design of experiment

Abstract Objective: Lopinavir (LPV), an antiretroviral protease inhibitor shows poor bioavailability because of poor aqueous solubility and extensive hepatic first-pass metabolism. The aim of the present work was to investigate the potential of the solid self-nanoemulsifying drug delivery system (S-SNEDDS) in improving dissolution rate and oral bioavailability of LPV. Materials and methods: Liquid SNEDDS (L-SNEDDS) of LPV were prepared using Capmul MCM C8, Cremophor RH 40 and propylene glycol and their amounts were optimized by Scheffe’s mixture design. L-SNEDDS formulations were evaluated for different physicochemical and in vitro drug release parameters. S-SNEDDS were prepared by adsorbing L-SNEDDS on Neusilin US2 and characterized for solid-state properties. In vivo bioavailability of S-SNEDDS, marketed Lopinavir + Ritonavir (LPV/RTV) formulation and pure LPV was studied in Wistar rats. Stability study of S-SNEDDS was performed as per ICH guidelines. Results and discussion: Optimized L-SNEDDS obtained by Scheffe design had drug loading 160 ± 1.15 mg, globule size 32.9 ± 1.45 nm and drug release >95% within 15 min. Solid state studies suggested the transformation of the crystalline drug to amorphous drug. The size and zeta potential of globules obtained on dilution S-SNEDDS remained similar to L-SNEEDS. In vivo bioavailability study revealed that S-SNEDDS has 2.97 and 1.54-folds higher bioavailability than pure LPV and LPV/RTV formulation, respectively. The optimized S-SNEDDS was found to be stable and had a shelf life of 2.85 years. Conclusion: The significant increase in drug dissolution and bioavailability by prepared SNEDDS suggest that the developed S-SNEDDS is a useful solid platform for improving oral bioavailability of poorly soluble LPV.

Nanomedicine-Based Gene Delivery for the Retina and Posterior Segment Diseases

The eye is an immune-privileged site and is more amenable to genetic therapy. A number of diseases in the posterior segment of the eye have genetic origin. The posterior segment of the eye is difficult to access. But routes to deliver drugs and genes have been worked upon. The genetic therapy ensures long-term treatment of the disease in the eye. The genes that are to be delivered to their proper site can be given through viral and non-viral vectors. Viral vectors offer a number of advantages when it comes to transfection efficiency and gene expression but are associated with immunity issues and cannot be loaded with genes which are more than 5 kb. Over the years non-viral gene vectors are becoming increasingly popular because of their higher gene loading capacity and number of distinct advantages over the viral vectors. But the genes that are to be delivered to the nucleus have to escape a number of degradative mechanisms outside and inside the cell to reach the nucleus. Lipoplexes and polyplexes have been successfully used in the treatment in nonclinical studies, but the clinical applications have still to see the light of the day.

Development and Characterization of Thermosensitive intranasal Gel Containing Paliperidone Loaded Microspheres

Purpose: The objective of the present investigation was to fabricate a thermosensitive gel containing paliperidone loaded microspheres for the treatment of schizophrenia for brain delivery through nasal route. Incorporation of drug in to microspheres and then in to gel should increase the duration of release and nasal duration time respectively. Material and Method: Ethyl cellulose microspheres containing paliperidone palmitate were prepared by emulsification of ethyl acetate dispersion containing polymer and drug with aqueous external phase containing polysorbate 80. Amount of ethyl cellulose and polysorbate 80 were identified as critical formulation variables influencing the drug release at critical time points, percentage yield and particle size. These factors were studied using 2 factors and 3 level face centered factorial design using Design Expert ® . Drug-excipient compatibility was ascertained using FTIR analysis. The paliperidone microspheres were then incorporated in to Pluronic F127 and HPMC gel having required thermo sensitive and muco adhesive properties. Gel containing microspheres was subjected to Ex vivo permeation study, irritation study using sheep nasal mucosa and pharmacodynamic study (spontaneous motor activity in mice). Results: Microspheres that could sustain the drug release up to 8 hours were developed. Thermoreversible gel having required thermo sensitive and muco adhesive properties was developed. The Ex vivo permeation study and pharm a codynamic study of the drug loaded microsphere containing gel confirmed the release up to 8 hours. The histopathology study showed absence of irritation on sheep nasal mucosa. Conclusion: Paliperidone palmitate loaded microspheres containing gel could prolong and target the drug release to brain and therefore give prolonged and intense action. Key words: Nose to brain delivery, Paliperidone palmitate, Pharmacodynamic activity, Thermoreversible gel, Desirability index.