Department of Saidla Faculty of Unani Medicine AMU Aligarh
The study was under taken to develop Sufoof-e-Muhazzil a Unani Pharmacopeial formulation well-known for its efficacy in the management of saman-e-mufrat (obesity) since centuries, in to advance tablet form for the better compliance of the patients. The different batches were developed after carry out the pre-compression study parameters and most appropriate batch was further selected for physico-chemical standardization. The standard operative procedures (SOPs) and in process quality control parameters were establish for reproducibility and to avoid batch to batch variation.The present study will pave the way for the further advancement of traditional dosage form and upgrade them to meet the criterion of emerging herbal pharmaceutical industry to provide the time tested safe and effective formulation to treat the obesity with the quality assured advance tablet in terms better compliance to end user.
The Unani system of medicine boasts a significant variety of single drugs and compound formulations that are effective and safe for the treatment of obesity. Several herbs documented in Unani classical literature are associated with weight reduction. However, there haven’t been any recent studies investigating their anti-obesity effects, despite their documented use in experiments and clinical trials. These include Luk-e- Maghsool, Muqil (Commiphora mukul Linn.), Kharkhask (Tribulus terrestris Linn.), Haldi (Curcuma longa Linn.) and Zeera Siyah (Carum carvi, Linn) etc.1 Sufoof-e-Muhazzil is among the most recognized formulations for addressing obesity within the Unani medical system. It is a polyherbal formulation used successfully by Unani physicians for the treatment of saman-e-mufrat (obesity) for ages. As outlined in the National Formulary of Unani Medicine, this formulation includes Ajwain/Nankhwah (Trachyspermum ammi Linn.,), Tukhm-e-karfas (Apium graveolens Linn), Sumbul-ut-Teeb (Nardostachys jatamansi), Gul-e-Surkh (Rosa damascene Mill.,), Marzanjosh (Origanum vulgare Linn.) and Luk-e-maghsool (Laccifer lacca). This pharmacopeial formulation is unmatched in its effectiveness for managing saman-e-mufrat (obesity). But the formulation is available in powder form which is a major hindrance to the patient’s compliance as well as mass acceptance. Therefore, in this study, the powdered dosage form of sufoof-e-muhazzil has been transformed into a tablet to enhance palatability, better patient compliance, and acceptance. This includes pharmaceutical analysis for quality assurance and development of SOPs for manufacturing standard operative procedure and further reference.
MATERIALS AND METHOD
The study aimed to redesign and develop Sufoof-e-Muhazzil into a tablet form, along with conducting its pharmaceutical analysis. The selected formulation, cited in Qarabadeen Hamdard, has significant therapeutic value for hyperlipidaemia and saman-e-mufrat (obesity). The ingredients for making Sufoof-e-Muhazzil mentioned in Qarabadeen Hamdard are listed in Table 1 below.
Table No. 1 Ingredients of Sufoof-e-Muhazzil 2
Procurement of raw Material, chemicals and excipients 1,4,5,6
The ingredients of sufoof-e-Muhazzil were procured from the drug store of Dawakhana Tibbiya College, Aligarh. All the drugs were identified and authenticated by Dr Huda Nafees, Dept of Saidla AMU. The specimen of single drugs and the tablet of sufoof-e-muhazzil have been deposited in the museum, Department of Saidla having voucher no. 2019 / 04 / S / AMU and 2019 / 04 / s / AMU–F.
The excipients and chemicals of the tablet of Sufoof-e-Muhazzil were procured from different companies, as mentioned below.
Preparation of tablets from the powder of Sufoof-e-Muhazzil 1,5,7
The drugs were first cleaned from all impurities (if any), present in them. After cleaning, crude drugs were dried in an oven at 40 ?C and coarse powder was obtained by grinding all the crude drugs. Then the obtained powder was sieved using sieve No. 120 and the fine powder was mixed with a binder (Acacia and maize). For wetting, distilled water was added to the mixture dropwise to make lubdi (dough). The mixture was then blended manually until a damp mass was obtained. The damp mass underwent granulation by being passed through sieve No. 16, after which the wet granules were collected in a stainless-steel tray. The granules thus prepared were dried in a hot air-drying oven (Tray Drier) for 30 minutes. Dried granules with glidant were subjected to compression by a multi-section rotatory press/tableting machine (20 stations single rotatory machine, at 6 Tons pressure for all batches. 1,8,9 (Table No. 6).
Composition of Tablet
The tablet was composed according to the formulation, where all the ingredients were powdered separately, mixed with excipients, and prepared by the compression method. After that, the prepared tablet was coated with a film-coating material. The ingredients of Sufoof-e-Muhazzil are mentioned in Table No. 2.
Table No. 2 Ingredients of Sufoof-e-Muhazzil 2
Table No. 3 Composition of Tablet of Sufoof-e-Muhazzil
Fig: 2 (a) Coated Tablets of Sufoof-e-Muhazzil
Fig: 2 (b) Uncoated Tablets of Sufoof-e-Muhazzil
The physiochemical parameters on which the redesigned tablet was evaluated are as follows:
Precompression evaluation of Tablets 1,5
Flow rate
50 grams of granules were taken, and a funnel was secured with its tip at a height of 10 cm above a piece of paper placed on a flat horizontal surface. Pour the material until the pile reaches a predetermined width. Rather than attempting to measure the angle of the resulting cone directly, divide the height by half the width of the base of the cone. The angle of repose (?) was calculated using the following formula:
Tan ? = h / r
Where: h is the height of the powder cone and r is the radius of the powder cone.
Fig 3: Angle of repose
Bulk density
The bulk density is the ratio of the mass of an untapped powder and its volume. The bulk density of the 20 gm granule blend was introduced into a dry 100 ml cylinder. The granules were carefully levelled without compacting, and the unsettled apparent volume V ? was measured. The bulk density was calculated using the formula.
Db = m / v ?
Where: m is the mass of the blend, v ? is the untapped volume.
Fig 4: Bulk density
Tapped density
To determine the tapped density, 20 g of granules were placed in a 100 ml measuring cylinder. After observing the initial volume, the sample was tapped for 20 minutes, and then the tapped volume was measured to the nearest graduated unit. The tapped density was calculated using the following equation:
Dt = m / vi
Where: m is the mass of the blend, Vi is the tapped volume
Fig 5: Tapped density Apparatus
Carr’s index
The Carr’s index is an indication of the compressibility of a powder.
Carr’s index was calculated with the formula,
C = 100 PT – PB / PT
Where PT is the tapped bulk density of the powder after tapping down and PB is the freely settled bulk density of the powder.
Fig 6: Carr’s Index
Hausner’s ratio
The Hausner’s ratio is a number that is correlated to the flowability of a powder or granule material. The Hausner's ratio is calculated by the formula,
H = PT / PB
Where PT is the tapped bulk density of the powder and PB is the freely settled bulk density of the powder.
Post-compression evaluation of Tablets 1,5
Organoleptic characters
Twenty tablets were examined for appearance, discolouration, and degradation through visual inspection. Additionally, they were assessed for aroma, taste, and texture.
Weight variation
Ten tablets were selected randomly and weighed individually using an electronic weighing machine to check for weight variation. The weight was expressed in mg. A ± 5?viation is acceptable for the tablets' average weight of 250 mg or more, hence this variation was considered appropriate.
Diameter of tablet
The uniformity of diameter was assessed by randomly picking three tablets, and the diameter was measured individually using a digital vernier calliper and expressed in mm.
Thickness of tablet
Uniformity of thickness was assessed by randomly picking three tablets, and the thickness was measured individually using a digital vernier calliper and expressed in mm.
Hardness of tablet
Hardness or tablet crushing strength (the force required to break a tablet in a diametric compression) was measured using Montsanto tablet hardness tester and expressed in kg/cm?2;.
Tablet disintegration
150 ml of distilled water at 37 ? ±1 was placed in the cylinders of the apparatus. 3-4 tablets were placed into the basket cautiously. The movement of the basket was maintained at the normal speed of the apparatus and 37 ? ±1 temperature. The time passed until no tablet was present, was noted, which gave the dispensability of the tablet in water. A time ranging from 7-8 minutes is satisfactory.
Friability test
Friability is the loss of weight of tablets in the container/package due to the removal of fine particles from the surface. The friability of the tablet is determined by using the Roche friabilator and expressed as a percentage. This device subjects the tablets to the combined effects of abrasion and shock in a plastic chamber revolving at 25 rpm and dropping the tablets from a height of 6 inches with each revolution. Pre-weighed samples of tablets were placed in the friabilator and subjected to 100 revolutions. The tablets were de-dusted using a soft muslin cloth and re-weighed. The friability is calculated by the formula.
F = 1- w ? / w × 100
Where w ? is the weight of the tablets after the test and w is the weight of the tablet before the test.
Fig 7: Friability apparatus
Dissolution Test
Fix the paddle or basket as per the test requirements. Set the temperature, RPM, and time according to the test requirements. Add the required volume of dissolution medium or buffer solution (900 mL) at pH 1.2, 4.8, and 6.8, employing the BK-RC6 station Dissolution Test Apparatus with a paddle stirrer at 50 RPM. Place the tablet in the jar or basket, maintaining the temperature at 37°C throughout. Switch on the mains and allow the dissolution to run. Collect the samples from the dissolution medium using a pipette at the required intervals. Replace the dissolution medium with the same amount of simulated fluid. Filter the samples using Whatman filter paper and check the absorbance under a UV spectrometer at wavelengths between 200-400 nm.
Fig: 8 (a) Dissolution Tester
Fig: 8 (b) Spectrophotometer
OBSERVATIONS AND RESULT
Physio-chemical standards of the tablet.
The following standards are for tablets. The data is based on multiple observations.
Physical appearance (Table No.4):
The colour of tablets was found to be Dark brown.
The odour of tablets was found to be slightly aromatic.
The taste of the tablet was found to be astringent.
Hard
Angle of repose:
The mean value of the angle of repose was found to be 30.71 ± 0.323 ?
Bulk density:
The mean value of bulk density was 0.437 ± 0.042 gm/ml.
Carr’s index:
The mean value of carr’s index was found to be 9.568 ± 0.941
(Table No. 5)
Hausner’s ratio:
The mean value of Hausner’s ratio was found to be 1.135 ± 0.004
Tablet hardness:
The mean value of tablet hardness was found to be 4.566 ± 0.026
Disintegration time:
The mean disintegration time was found to be 8 ± 0.816 minutes
Weight loss (Friability test):
The mean weight loss was found to be 5.646 ± 0.03 gm (Table No. 6)
Weight variation:
The mean weight was found to be 0.525 ± 0.01g
Uniformity of Diameter; 13.54 ± 0.00 mm
Thickness:
4.77 ± 0.01 mm (Table No. 7)
Absorbance (Dissolution Test):
The absorbance of the formulation is shown in Table No. 12 and Fig 9 a, b, c.
Table No. 4 Organoleptic characteristics of Tablets
Table No. 5 Result of the angle of repose, bulk and tapped density, carr’s index
Table No. 6 Result of Hausner’s ratio, disintegration time, hardness, friability
Table No. 7 Result of weight variation, Uniformity of diameter, Thickness
Table No. 8 Composition of Uncoated Tablet
Table No. 9 Composition of each Uncoated Tablet
Table No. 10 Composition of coated tablet
Table No. 11 Composition of each coated tablet
Table No. 12 Lab data of Absorbance of Sufoof-e-muhazzil tablet in different PH of buffer solution
Fig: 9 (a) Dissolution graph of sufoof-e-muhazzil tablet in PH 1.
Fig: 9 (b) Dissolution graph of sufoof-e-muhazzil tablet in PH 6.8
Fig: 9 (b) Dissolution graph of sufoof-e-muhazzil tablet in PH 5.6
DISCUSSION
Obesity is one of the oldest documented metabolic disorders in recorded history. The abnormality has persisted throughout the centuries. Similarly, a large portion of the population, both obese and non-obese, suffers from hyperlipidaemia and associated disorders such as atherosclerosis and heart diseases. Most of the obese suffer from hyperlipidaemia, and the majority of those with hyperlipidaemia also suffer from obesity. 10 Although these two disorders have been vividly described in ancient literature and suitable drugs have been reported for their management, this disease still persists and is becoming increasingly common. It is recognized as one of the major public health problems worldwide.11 According to the WHO, in 2016, more than 1.9 billion adults, 18 years and older, were overweight. Among these, over 650 million were obese. In 2016, 39% of adults aged 18 years and over (39% of men and 40% of women) were overweight. Overall, about 13% of the world’s adult population (11% of men and 15% of women) were obese in 2016. The worldwide prevalence of obesity nearly tripled between 1975 and 2016. In 2019, an estimated 38.22 million children under the age of 5 years were overweight or obese. Saman-e-mufrat (obesity) is emerging as an important health challenge in India. The national family health survey (N.F.H.S) shows that 12.1% men and 14.8% women in India are overweight or obese. In Africa, the number of overweight under 5 has increased by nearly 24% since 2000. 11,12 Though some developments in this field have been made and many drugs have been invented after extensive research, the disease is still uncontrollable. The reason behind the failure of therapy, or at least not achieving the expected target, lies in the fact that the treatment is not devoid of risk factors and toxicity on one hand, and the drugs are exorbitantly costly on the other, leading to the withdrawal of therapy before the disease is cured. The Unani system of medicine claims to possess many drugs that are stated to be effective in treating obesity and hyperlipidaemia. However, it is a great irony that such agents, despite being extensively used successfully in clinical practice by Unani physicians, have not attracted the attention of research workers and have not been evaluated scientifically. Therefore, they have not found a place in general practice. Sufoof-e-Muhazzil is such a poly pharmaceutical formulation of repute, which is clinically used as anti-obesity drug without any important side effects. The modification of classical, time-tested dosage forms can be debatable. Earlier Unani and Arab physicians also experimented extensively with dosage forms. There is a dire need to study classical dosage forms and redesign them into advanced forms for better compliance and to meet global market demand. Additionally, the pharmacological study of developed formulations is necessary to determine their safety and efficacy, as well as to assess the effect of redesigning on their pharmacological activity and other aspects of the formulation. These types of studies can reveal the added benefits of newly developed dosage forms or validate the classical methods. The sufoof-e-muhazzil is beneficial in hyperlipidaemia but many problems are encountered during its usage in sufoof form such as it has bitter taste, nauseating smell, no dose accuracy, bulky, difficulty in preparation, and its ingredients are not easily available. Tablets offer a novel approach as they provide advantages such as accuracy and uniformity in weight compared to powders. Tablets are one of the most convenient solid dosage forms, offering an accurately measured dose in a portable package. They can be designed to protect the medication or disguise unpleasant ingredients. Tablets are the most stable of all oral dosage forms and are easy to swallow; they are also very economical. The cost of the formulation is reduced because it is easy to manufacture on a large scale. Hence, it is better to redesign the sufoof into tablet form for improved acceptability and compliance among patients. The prepared tablets were evaluated for organoleptic characteristics as the first step to identify the drugs and to indicate the status and condition of the drug. If any discoloration or black spots appear, it shows degradation or decomposition in the tablet. Organoleptic properties such as colour, taste, odour, appearance, and texture were noted and are depicted in the table. Manufacturing of good quality tablets initially starts from direct compression of the formulation powder. Different fillers (in different proportion), disintegrants, binders, lubricant desiccant, etc., are used in the formulation for making the granules. The pre-compression parameters of all the batches were evaluated. Proper granulation methods were adopted, and granulation was done manually with the help of the guidelines. Different batches of the tablets were made using the trial-and-error method. The most suitable and optimized batch was subjected to pharmaceutical analysis and demonstrated good results. The selected batch displayed good pre-compression properties. The bulk density and tapped density were 0.437 ± 0.042 and 0.871 ± 0.0069, respectively. The Carr’s Index was 9.568 ± 0.941, which is below 23 and indicates good flow properties. The Hausner’s ratio was 1.135, which is within the good range for flow type. The angle of repose was 30.71 ± 0.323, which is also within the good range. One of the major challenges of powdered drug is proper flowability which is very important in the processing of powders particularly when tablets are compressed in high-speed tablet press. Post-compression parameters such as, hardness, friability, disintegration time were 4.566±0.026 kg/cm?2;, 0.056%, and 8±0.816mints respectively. It may be concluded that, from the mentioned ingredients/excipients and process, we can produce tablets with high kinetic and dynamic quality that meet the analytical specifications. Tablets made from powder are currently the most popular form of dosage on the market. This work is a step toward the upliftment of classical Unani formulations. The dose, compared to the classical formulation, has been reduced from 22.5 grams of unpleasant powder to three tablets, each weighing approximately 500 mg. This makes them easy to swallow and facilitates compliance with the regimen. Patients tend to prefer medicines that are easily accessible, feasible, and affordable. Some formulations are not taken by patients because they are difficult to consume. Tablets require a certain amount of strength or hardness and resistance to friability to withstand mechanical shocks during manufacture, packaging, shipping, and handling by both pharmacists and patients. The resistance of the tablet to chipping, abrasion, or breakage under the aforementioned conditions before use depends on its hardness and friability. Hardness and minimal friability indicate that tablets have good mechanical resistance and the ability to withstand abrasion. A loss of less than 1% is considered acceptable by industrial standard and all the tablets were found well within the approved range to give good handling properties without breakage or excessive friable problems.5,9 Tablets should be hard enough to withstand the manufacturing, packaging, and transportation processes. However, they cannot be too hard, as this may alter the disintegration or release of the drug product. Disintegration roughly indicates the potential pattern of dissolution of the active substance. Hence, the experimental conditions should closely mimic the situations that a tablet encounters in the gastrointestinal tract, in terms of temperature, pH, and mechanics. Physical parameters such as area, hardness, surface characteristics, and size can significantly affect the rate of disintegration of drugs contained in a complex system. After administration, the tablet should disintegrate readily for quick absorption in the gastrointestinal tract. Therefore, the tablets were also subjected to evaluation of disintegration time. According to the specifications, the tablet must disintegrate and all particles must pass through a 10-mesh screen within the specified time. If any residue remains, it must be a soft mass. It is stated that uncoated tablets must disintegrate in not more than 45 minutes. 6, 9, 13 Therefore, in view of the above and to achieve global acceptance, a modification has been made to the pharmaceutical Unani formulation Sufoof-e-Muhazzil, converting it into tablet form. In this study, we focused on remodelling Sufoof-e-Muhazzil into a tablet, which not only meets all modern criteria for palatability, quality, and pre- and post-formulation studies but will also play a pivotal role in addressing major challenges. It will pave the way for the reorganization and acceptance of an effective formulation for successful health care management. Standard Operating Procedures (SOPs) for the manufacturing process, along with relevant pharmaceutical aspects, have been documented for future reference. The developed dosage form may be subjected to further experimentation and clinical studies to assess its efficacy.
CONCLUSION
The study assumes great significance and will provide key diagnostic characteristics specifically applied for the standardization of the formulation, such as organoleptic properties, pre-compression studies, dissolution, and disintegration. These serve as important tools for establishing standards for quality assurance. The study also offers an improvement in the Unani health system by redesigning the less convenient powder form into a more convenient tablet form. The observations obtained from the various physico-chemical tests of lab samples of the redesigned Sufoof-e-Muhazzil tablets may serve as a standard reference for future batches.
REFERENCES
Qazi Zaid Ahmad , Saima Aslam, Zarin Fatima, Azizur Rahman, Mohammad Rashid, From Powder to Pill: The Development of Sufoof-e-Muhazzil into Tablet for Weight Management, Int. J. of Pharm. Sci., 2024, Vol 2, Issue 8, 3104-3116. https://doi.org/10.5281/zenodo.13316901
10.5281/zenodo.13316901
