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پیار کے دیپ جلاتی ہوئی پاگل لڑکی

پیار کے دیپ جلاتی ہوئی پاگل لڑکی
کوچۂ عشق میں جاتی ہوئی پاگل لڑکی

جس کو اَن دیکھے جزیروں کی تمنا ہے بہت
باتیں اس ڈھب کی بناتی ہوئی پاگل لڑکی

وہ فقط مجھ کو سنانے کی لگن رکھتی ہے
گیت جھرنوں کے سے گاتی ہوئی پاگل لڑکی

آس کی ڈور سے جینے کا ہنر جانتی ہے
کھلکھلاتی سی، ہنساتی ہوئی پاگل لڑکی

ہے وہ تتلی سی ، گھٹا سی کہ فضاؔ کے جیسے
موسموں کو وہ لبھاتی ہوئی پاگل لڑکی

Shibli, English, and the Step-Mother

The relationship between English (in what this term comes to mean as a language, as a discipline of studies, and as a synecdoche of Western culture) and our culture as Muslim Pakistanis has developed over a period of time since the British colonization. The history of this cultural interaction may be divided into three broad phases: the initial, the middle, and the present. The strategy adopted in this paper is based upon the argument that this relationship may be traced through some of the most representative figures of our culture, such as, Shibli, Iqbal, Faiz etc. In each phase of this interaction. The present essay on Shibli deals with the first phase of our cultural interaction with English. It adopts what may be termed as an analogical approach to the issue as it intends to engage with what I think to be rather unwarranted psychoanalytic forays of some of our critics into the psycho-dynamics of such culturally representative figures like Shibli in their relationship with English. The paper exploits the analogy first used by Sheikh Muhammad Ikram, and later employed by Nasir Abbas Nayyar that Shibli’s attitude towards English was the same as his attitude towards his step-mother at home. English, in other words, was a step-mother for Shibli, and for the generations represented through his figure in this early phase of our cultural interaction with the language. Shibli’s terms of engagement with his step-mother, and analogically with English, is the subject of this essay.

Formulation, Characterization and Pharmacokinetic Evaluation of Statistically Optimized Solid Lipid Microparticles of Cardiovascular Drugs

The use of Ivabradine (IBH) and Nebivolol (NEB) are considered as being effective and safe but their short plasma half-life and decreased bioavailability in conventional formulations demand frequent dosing which ultimately reduce patient compliance. The purpose of this research was to prepare Solid lipid microparticles (SLMs) of IBH and NEB to overcome the inadequacies associated with conventional formulation and to release drugs in a sustained fashion. Preliminary studies were performed to identify the effect of independent variables like concentration of lipid polymer like beeswax (BW), carnaubawax (CW), stearic acid (St-A), Glyceryle monostearate (GMS) and surfactant like tween 20 (T-20) and tween 80 (T-80). IBH and NEB loaded SLMs were designed in five different batches with different concentrations of a single or combination of lipid polymer by simple melt emulsification technique and solvent evaporation method. Central composite Rotatable Design (CCRD) was applied on every batch of SLMs to study the impact of three independent variables on responses like percentage yield (Y1), entrapment efficiency-EE-(Y2) and drug release (Y3) at pH 6.8 for 12hr. In every batch of SLMs, the compatibility of drugs with lipid polymer was checked by Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and X-ray powder Diffractometry (XRD). SLMs were further analyzed for rheological behavior, zeta potential, size and for morphology by scanning electron microscope (SEM).The drug release data was analyzed by different kinetic models. Numerical optimization techniques were applied and an optimized formulation (OF) from every batch (total 5 optimized formulations) were further prepared and then characterized for in-vitro and in-vivo pharmacokinetic behaviour in healthy male volunteers. Before performing in-vivo drug analysis, HPLC method for the simultaneous estimation of IBH and NEB was developed and validated for linearity and range, intra- and inter-day precision, accuracy, recovery, limit of detection and limit of quantification. The experimental conditions of HPLC method were optimized by using CCRD, in which, flow rate, pH of buffer and wavelength were used as independent factors in order to optimize three dependent factors like retention time, number of theoretical plates and tailing factor of NEB and IBH. Noncompartmental model approach was used to calculate the pharmacokinetic parameters including the area under the plasma concentration–time curve from zero to infinity (AUC0-∞), Tmax, Cmax, t1/2, MRT and kel. All data was expressed as mean ± SD (standard deviation). Spherical, smooth surface SLMs having good rheological behavior were obtained. The resultant data from FTIR, DSC and XRD concluded the absence of any interaction between formulation components. Zeta-potential study confirmed better stability of optimized SLMs because of presence of negative charge on OF1 (-30mV to 52mV), OF2 (-25mV to -60mV), OF3 (-20mV-40mV), OF4 (-20mV to -40mV) and OF5 (-40 to -60). The size of SLMs ranged from ranged from 300µm to 400µm (OF1), 20µm to 120µm (OF2), 80µm to 220µm (OF3), 20µm to 100µm (OF4) and from 05µm to 20µm (OF5). The SLMs prepared from solvent evaporation technique (OF2, OF4, OF5) were found to have smaller size with smoother spherical surface as compared to SLMs (OF1) produced by simple emulsion congealing technique. The dependent variables had followed quadratic, 2F1 and linear models. The obtained outcomes of Y1, Y2 and Y3 for all of the SLMs have shown a significant dependence on formulation conditions. The Y1 and Y2 were found to be varied from 38 to 90% and 29 to 78% indicating the effect of formulation variables. The drug release Y3 was found to be 46 -88% and was significantly (p˂0.05) affected by lipid polymer concentration. The release mechanism followed the zero order and Korsmeyer-Peppas (n˃0.85) kinetic models suggesting slow erosion alongwith diffusion mechanism. A highly precise, robust, economical, specific, sensitive, less time consuming and accurate HPLC method was successfully developed and validated in mobile phase and human plasma as evident from short retention time and run time. The mobile phase consisting of mixture of acetonitrile and phosphate buffer maintained at pH of 3.5 in the volumetric ratio of 1:1 led to achievement of the best resolution. The optimized HPLC experimental conditions involve a flow rate of 1 mL/min under which, a good retention time of 3.591 minutes for NEB and 2.21 minutes for IBH was obtained. The optimized SLMs OF3 (Group C), OF4 (Group D) and OF5 (Group E) have significantly higher (P˂0.005) Cmax, Tmax, AUC0-24, MRT0-24 and t1/2 than those obtained from OF1 (Group A) and OF2 (Group B) because of use of a combination of lipid polymers. However, OF1 and OF2 were found to be better as compared to marketed brands of IBH (Group F) and NEB (Group G).The difference in Tmax, AUC0-24, MRT0-24 for OF3, OF4, OF5 was found to be statistically insignificant, however these parameters were found to be higher for OF5. The marketed brands of IBH and NEB released the drugs immediately resulting in rapid drug absorption with lower Tmax and lower AUC values. Results of the study clearly depicted the suitability of lipids as carriers for designing a controlled release SLMs which would definitely increase the clinical utility of IBH and NEB to improve the patient compliance by decreasing dosing frequency and drugs associated side effects particularly in the cases of chronic illnesses like Hypertension. The results of pharmacokinetic analysis were quite suggestive of prominent effect of SLM formulations on in-vivo behavior of drugs and they can be considered a prospective administration system for once-a-day oral administration of a medicament. Key Words: Beeswax, Carnauba wax, Central composite rotatable design (CCRD), DSC, FTIR, Glyceryle monostearate, HPLC, Ivabradine, Melt Emulsion Congealing Technique, Nebivolol, Solid Lipid Microparticles, Solvent evaporation process, Stearic acid, XRD.
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