پہلا ستارہ
آفتاب نواب
کسی بھی فنکار کے فنی سفر کا پہلا قدم اظہار کے میڈیم کی تلاش ہے۔ اس مرحلے کا طے ہونا جز ثابت ذہنی سے تفکر کے ممکن نہیں۔ ڈاکٹر فہد ملک اس مرحلے پر مبارک باد کے مستحق ہیںکہ وہ اپنے اظہار کا ذریعہ تلاش کرنے میں کامیاب ہو چکے ہیں۔ کسی بھی زبان میں شعر اس وقت تخلیق ہوتا ہے جب وہ اتنی طاقت ور ہو چکی ہو کہ اس کے پاس رمز و ایما کے تمام وسائل آچکے ہوں اور آدمی تب شعر کہہ سکتا ہے جب اس کے اندر رمز و ایما سما سکتے ہوں، پک سکتے ہوں اور لفظوں میں ڈھل سکتے ہوں۔ فہد ملک رمز و ایما کی طرف سفر پر نکلے۔ اس کتاب میں آپ کی ملاقات جس فہد ملک سے ہو گی وہ انسان کو سہل نہیں جانتا۔ محبت کو سچے جذبے سے تعبیر کرتا ہے۔ اخلاص و رواداری ،حریت، سماجی جدلیات اور انسان کی باطنی کیفیات پر غور کرتا ہے۔ فنکار اپنی کائنات خود بناتا ہے اور فہد نے اپنے کائنات شعر میں بنانے کا فیصلہ کیا ہے جس کا پہلا ستارہ یہ کتاب ہے۔
اس کتاب میں کرافٹ کی طرف متوجہ ہونے ، فکر کو خاص سطح تک لے جانے کی کاوش کے نقوش ملتے ہیں۔ اس امر کو مدِ نظر رکھتے ہوئے یہ کہا جاسکتا ہے کہ فہد ملک آئندہ وقت کا دل پذیر صاحبِ سخن ہے۔
The examination of tax compliance expenses is becoming more relevant, revealing a complex challenge that involves both national and international fiscal policies. This matter is closely linked to tax evasion and avoidance, and its consequences could distort taxpayers' economic choices. Against this background, the study focuses on the impact of profit tax on the operational outcomes of the 'Fortalecida Abel Santamaría Cuadrado' Credit and Services Cooperative, which operates within the sugarcane sector in Camagüey, Cuba. The research uses both qualitative and quantitative methodologies to investigate this issue. The study aims to provide a detailed understanding of how tax compliance costs affect the cooperative in question by implementing a tripartite procedure that uses mathematical techniques and relative frequency analysis. A key finding from this investigation is the negative impact resulting from the exclusion of advance salary payments as deductible expenses in tax calculations. This finding highlights a critical area for fiscal policy reform as the policy oversight is identified as a source of financial strain for the cooperative. The implications of this discovery are far-reaching, indicating that similar cooperatives and businesses within Cuba (and possibly in comparable economic contexts) may also be experiencing analogous fiscal burdens.
Based on these insights, the study recommends the creation of customized methodologies to accurately measure tax compliance costs in the Cuban context. These methodologies should consider the distinctive socio-economic and regulatory features that define the Cuban economy, allowing for more precise evaluations of tax-related burdens on businesses. Furthermore, this research invites broader contemplation on the intersection of tax policy and business sustainability, particularly within sectors that are crucial to national economies but may be vulnerable to strict tax regimes. It emphasizes the need for a balanced approach to tax legislation that protects revenue interests without impeding economic vitality.
Formulation Development and in-vivo Performance of Pharmaceutical Cocrystals The use of soluble cocrystal for delivering drugs with low solubility, although a potentially effective approach, often suffer from the problem of rapid disproportionation during dissolution, which negates the solubility advantages offered by the cocrystal. This necessitates their robust stabilization in order for successful use in a tablet dosage form. The cocrystal between carbamezepine and succinic acid (CBZ-SUC) exhibits a higher aqueous solubility than its dihydrate, which is the stable form in water. Using this model system, I demonstrate an efficient and material-sparing tablet formulation screening approach enabled by intrinsic dissolution rate measurements. Three tablet formulations capable of stabilizing the cocrystals both under accelerated condition of 40oC and 75% RH and during dissolution were developed using three different polymers, Soluplus® (F1), Kollidon VA/64 (F2) and Hydroxypropyl methyl cellulose Acetate sucinate (F3). When compared to a marketed product, Epitol® 200 mg tablets (F0), drug release after 60 min from formulations F1 (~82%), F2 (~95%) and F3 (~95%) was all higher than that from Epitol® (79%) in a modified simulated intestinal fluid. Studies in albino rabbits showed correspondingly better bioavailability of F1 – F3 than Epitol® tablets. All the three experimental formulations gave statistically significant improvements in AUC0-72 of CBZ than Epitol tablets by applying ANOVA followed by Tukey’s post hoc test (*P˂0.05 for F0-F1, ***P˂0.05 F0-F2, ***P˂0.05 F0-F3). Among the three formulations, F2 tablet formation was the best based on both in-vitro and in-vivo evaluations. Towards the second formulation approach, I first used common polymers to study the supersaturation of carbamezepine-succinic acid (CBZ-SUC) cocrystal at different conditions. In-situ Raman spectroscopy was used to monitor the solid phase during dissolution studies. The solid phase at the end of each experiment was characterized by FTIR and powder X-Ray diffractometry. In-vivo study was performed on selected xi suspension formulations. In absence of polymers, no dissolution advantage was attained by cocrystals due to rapid crystallization of CBZ dihydrate. At room temperature Polyvinyl pyrrolidone (PVP) at concentration of 2% w/v did not stabilize the supersaturated solution, whereas polymer concentration of 0.025% w/v hydroxypropyl methyl cellulose acetate succinate (HPMCAS) stabilized the cocrystal and enhanced the solubility of CBZ in buffer solution at pH 6.8 by 3.2folds to that of stable dihydrate form. A formulation of CBZ-SUC cocrystal containing HPMCAS as a crystallization inhibitor and soluplus® as solubilizer, superior in-vitro dissolution performance was achieved compare to pure CBZ having similar composition at 37±1Ċ. Pharmacokinetic studies in rabbits showed that one of the formulations F7-X (1% w/v cocrystal, 1% w/v HPMCAS and 2% w/v soluplus®), caused around 6folds enhancement in AUC0-72 (***P˂ 0.05), and also led to a much higher Cmax of 4.73 μg/mL than 1.07 μg/mL Cmax of ‘neat’ cocrystal given orally. Also, the F7-X outperformed a reference formulation of CBZ by {1.37folds AUC0-72 of cocrystal formulation (***P˂ 0.05) and Cmax of 3.9 μg/mL} with similar composition to F7-X.